CHRNA4 (P43681) variants and mutations
CHRNA4 (also known as P43681) is a human protein-coding gene encoding a neuronal acetylcholine receptor subunit alpha-4 protein. It contributes to neuronal nicotinic acetylcholine responses that regulate excitability and neurotransmitter release. Dominant gain-of-function variants classically cause sleep-related hypermotor epilepsy, formerly termed autosomal dominant nocturnal frontal-lobe epilepsy. This analysis covers 1,393 CHRNA4 variants and mutations. Of these, 85% have computational variant effect predictions. Disease context includes nicotine dependence, autosomal dominant nocturnal frontal lobe epilepsy, and chronic obstructive pulmonary disease. Example CHRNA4 variants include M1L, M1T, and E2D.
Variant analysis overview
- Gene: CHRNA4
- Protein: P43681
- UniProt accession: P43681
- Organism: Homo sapiens
- Variants analyzed: 1393
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 999 unspecified-consequence records; 27 frameshift variants; 218 missense variants; 129 synonymous variants; 14 stop-gained variants; 2 in-frame deletions; 1 splice-region variants; 1 in-frame insertions; 2 substitution
- Prediction scores: 1,186 variants have prediction scores (85% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: nicotine dependence, autosomal dominant nocturnal frontal lobe epilepsy, chronic obstructive pulmonary disease, smoking cessation, familial sleep-related hypermotor epilepsy, smoking initiation, lung cancer, smoking behavior, hereditary disease, chronic lung disease, bronchus cancer, chronic bronchitis.
Protein structure and variant hotspots
- Protein features: 4 transmembrane segments; 2 binding sites; 6 post-translational modification sites.
- Structural context: 124 variants have structural context.
- PTM context: 13 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable CHRNA4 variants
Examples include M1L, M1T, E2D, E2G, E2Q, L3Q, L3R, G4R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs1359272155, ClinGen CA409645106, ClinVar RCV001937202, MetaLR 0.24, MetaSVM -0.80, Uncertain significance, Familial sleep-related hypermotor epilepsy
- M1T (p.Met1Thr), rs2068814460, ClinGen CA409645100, ClinVar RCV001822062, ClinVar RCV001869649, MetaLR 0.28, MetaSVM -0.73, Uncertain significance, Familial sleep-related hypermotor epilepsy; CHRNA4-related disorder; not provide
- E2D (p.Glu2Asp), TOPMed rs1244424506, REVEL 0.17, CADD 18.40
- E2G (p.Glu2Gly), Ensembl rs2068814434, REVEL 0.22, CADD 23.00
- E2Q (p.Glu2Gln), rs2145412501, ClinGen CA409645080, ClinVar RCV001923138, Ensembl rs2145412501, AlphaMissense 0.12, MetaLR 0.24, Uncertain significance, Familial sleep-related hypermotor epilepsy
- L3Q (p.Leu3Gln), rs2145412488, ClinGen CA409645055, ClinVar RCV001933947, ClinVar RCV004975937, REVEL 0.26, AlphaMissense 0.07, Uncertain significance, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases
- L3R (p.Leu3Arg), rs2145412488, ClinGen CA409645050, ClinVar RCV001560283, Ensembl rs2145412488, AlphaMissense 0.07, MetaLR 0.27, Uncertain significance, not provided
- G4R (p.Gly4Arg), gnomAD rs2068814329, REVEL 0.15, CADD 13.50
- G5D (p.Gly5Asp), TOPMed rs946142547, gnomAD rs946142547, REVEL 0.42, CADD 19.90, Uncertain significance, Familial sleep-related hypermotor epilepsy
- G5S (p.Gly5Ser), rs1043176387, ClinGen CA317447596, ClinVar RCV001059426, ClinVar RCV002489657, REVEL 0.25, CADD 16.50, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; Autosomal dominant nocturnal frontal
- G5V (p.Gly5Val), rs946142547, ClinGen CA317447591, ClinVar RCV001348152, ClinVar RCV004968099, REVEL 0.35, CADD 18.70, Uncertain significance, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases
- P6A (p.Pro6Ala), rs796052312, ClinGen CA317447587, ClinVar RCV001507474, TOPMed rs796052312, REVEL 0.14, CADD 9.17, Uncertain significance, not provided
- P6L (p.Pro6Leu), rs1238575890, ClinGen CA409645003, ClinVar RCV000560700, TOPMed rs1238575890, REVEL 0.19, CADD 18.00, Likely benign, Familial sleep-related hypermotor epilepsy
- P6S (p.Pro6Ser), rs796052312, ClinGen CA313532, ClinVar RCV000186917, ClinVar RCV001443486, REVEL 0.13, CADD 10.80, Likely benign, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases; not provide
- P6T (p.Pro6Thr), rs796052312, ClinGen CA409645010, ClinVar RCV000615300, ClinVar RCV001036986, REVEL 0.12, CADD 14.70, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not specified
- G7A (p.Gly7Ala), rs1025632281, ClinGen CA317447573, ClinVar RCV000811097, ClinVar RCV001766694, REVEL 0.22, CADD 18.80, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- G7E (p.Gly7Glu), rs1025632281, ClinGen CA409644990, ClinVar RCV003746314, TOPMed rs1025632281, REVEL 0.32, CADD 21.90, Uncertain significance, Familial sleep-related hypermotor epilepsy
- G7R (p.Gly7Arg), rs1330177627, ClinGen CA409645001, ClinVar RCV003746774, gnomAD rs1330177627, REVEL 0.34, CADD 17.70, Uncertain significance, Familial sleep-related hypermotor epilepsy
- A8T (p.Ala8Thr), gnomAD rs1228141086, REVEL 0.18, CADD 11.70
- P9L (p.Pro9Leu), TOPMed rs1457939971, REVEL 0.11, CADD 20.40
- P9Q (p.Pro9Gln), TOPMed rs1457939971, REVEL 0.13, CADD 15.90
- P9S (p.Pro9Ser), rs2516580191, ClinGen CA409644957, ClinVar RCV003746741, ClinVar RCV005806801, REVEL 0.13, CADD 16.00, Conflicting interpretations, Inborn genetic diseases; Familial sleep-related hypermotor epilepsy
- R10P (p.Arg10Pro), TOPMed rs1285617924, gnomAD rs1285617924
- R10Q (p.Arg10Gln), TOPMed rs1285617924, gnomAD rs1285617924, REVEL 0.12, CADD 5.25
- R10G (p.Arg10Gly), rs2068813671, ClinGen CA409644949, ClinVar RCV001891475, TOPMed rs2068813671, AlphaMissense 0.08, MetaLR 0.21, Uncertain significance, Familial sleep-related hypermotor epilepsy
- R10L (p.Arg10Leu), rs2516580169, ClinGen CA2739277232, ClinVar RCV003747120, REVEL 0.14, CADD 6.67, Uncertain significance, Familial sleep-related hypermotor epilepsy
- L11V (p.Leu11Val), TOPMed rs1330153997, gnomAD rs1330153997, REVEL 0.20, CADD 13.00
- L12P (p.Leu12Pro), rs1060503516, ClinGen CA16616249, ClinVar RCV000464089, ClinVar RCV001290671, REVEL 0.34, CADD 7.41, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not specified
- P13L (p.Pro13Leu), rs796052313, ClinGen CA409644897, ClinVar RCV003746693, REVEL 0.09, CADD 7.96, Likely benign, Familial sleep-related hypermotor epilepsy
- P13R (p.Pro13Arg), rs796052313, ClinGen CA313534, ClinVar RCV000186918, ClinVar RCV001068685, REVEL 0.12, CADD 8.79, Likely benign, Familial sleep-related hypermotor epilepsy; not specified
- P14L (p.Pro14Leu), rs761934698, ClinGen CA313536, ClinVar RCV000654330, ClinVar RCV001704973, REVEL 0.11, CADD 3.79, Likely benign, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases; not provide
- P14T (p.Pro14Thr), Ensembl rs1555841119, REVEL 0.14, CADD 7.57
- L15P (p.Leu15Pro), rs886044055, ClinGen CA10606290, ClinVar RCV000325560, ClinVar RCV001850435, REVEL 0.53, CADD 22.50, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- L15R (p.Leu15Arg), 1000Genomes rs886044055, TOPMed rs886044055, Uncertain significance, Familial sleep-related hypermotor epilepsy
- L18R (p.Leu18Arg), rs796052314, ClinGen CA313538, ClinVar RCV000186920, ClinVar RCV005089937, REVEL 0.55, CADD 21.60, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not specified
- L19R (p.Leu19Arg), TOPMed rs2068812686
- G20E (p.Gly20Glu), TOPMed rs1196825724, gnomAD rs1196825724, REVEL 0.38, CADD 15.10
- T21A (p.Thr21Ala), TOPMed rs2068812501, REVEL 0.08, CADD 3.91
- T21P (p.Thr21Pro), TOPMed rs2068812501
- G22C (p.Gly22Cys), gnomAD rs1208604806, REVEL 0.31, CADD 14.50
- G22S (p.Gly22Ser), gnomAD rs1208604806, REVEL 0.09, CADD 9.69, Uncertain significance, not provided
- L23I (p.Leu23Ile), Ensembl rs1555841109, REVEL 0.08, CADD 12.90
- R25=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- R25C (p.Arg25Cys), rs2068812315, ClinGen CA409644756, ClinVar RCV001418435, Ensembl rs2068812315, REVEL 0.22, CADD 21.10, Likely benign, Familial sleep-related hypermotor epilepsy
- R25H (p.Arg25His), rs1262817628, ClinGen CA409644752, ClinVar RCV003746140, REVEL 0.21, CADD 15.60, Uncertain significance, Familial sleep-related hypermotor epilepsy
- R25L (p.Arg25Leu), TOPMed rs1262817628, gnomAD rs1262817628, REVEL 0.11, CADD 14.00
- A26D (p.Ala26Asp), ExAC rs761362001, TOPMed rs761362001, gnomAD rs761362001, REVEL 0.34, CADD 1.80, Uncertain significance
- A26G (p.Ala26Gly), ExAC rs761362001, TOPMed rs761362001, gnomAD rs761362001, REVEL 0.17, CADD 0.25, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases
- A26V (p.Ala26Val), rs761362001, ClinGen CA409644096, ClinVar RCV000701713, ClinVar RCV004777847, REVEL 0.16, CADD 0.51, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- S27R (p.Ser27Arg), rs1211831892, ClinGen CA409644087, ClinVar RCV001769253, ClinVar RCV003583199, REVEL 0.07, CADD 14.60, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- S27T (p.Ser27Thr), ExAC rs776391457, gnomAD rs776391457, REVEL 0.05, CADD 5.58
- S28C (p.Ser28Cys), ExAC rs768015799, gnomAD rs768015799, REVEL 0.07, CADD 11.10
- S28G (p.Ser28Gly), ExAC rs768015799, gnomAD rs768015799, REVEL 0.03, CADD 7.59
- S28R (p.Ser28Arg), ExAC rs768015799, gnomAD rs768015799
- H29R (p.His29Arg), gnomAD rs1483174024, REVEL 0.04, CADD 14.30
- H29Y (p.His29Tyr), rs2516573562, ClinGen CA409644064, ClinVar RCV002447981, Uncertain significance, Inborn genetic diseases
- V30L (p.Val30Leu), rs746557446, ClinGen CA9957976, ClinVar RCV001322247, ExAC rs746557446, REVEL 0.03, CADD 11.40, Uncertain significance, Familial sleep-related hypermotor epilepsy
- V30M (p.Val30Met), rs746557446, ClinGen CA313603, ClinVar RCV000186962, ClinVar RCV001374314, REVEL 0.03, CADD 13.70, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not provided
- E31* (p.Glu31Ter), Ensembl rs2068775541
- E31A (p.Glu31Ala), Ensembl rs2068775482
- T32N (p.Thr32Asn), rs200601170, ClinGen CA9957975, ClinVar RCV001489590, 1000Genomes rs200601170, REVEL 0.05, CADD 23.40, Likely benign, Familial sleep-related hypermotor epilepsy
- R33G (p.Arg33Gly), ESP rs370553755, ExAC rs370553755, gnomAD rs370553755, Uncertain significance
- R33L (p.Arg33Leu), NCI-TCGA Cosmic COSV1009, 1000Genomes rs201575409, ExAC rs201575409, Uncertain significance
- R33P (p.Arg33Pro), rs201575409, ClinGen CA317446017, ClinVar RCV000711168, 1000Genomes rs201575409, REVEL 0.41, CADD 22.30, Uncertain significance, not provided
- R33Q (p.Arg33Gln), rs201575409, NCI-TCGA Cosmic COSV1009, 1000Genomes rs201575409, REVEL 0.12, CADD 21.80, Uncertain significance, Familial sleep-related hypermotor epilepsy
- R33W (p.Arg33Trp), rs370553755, ClinGen CA9957974, ClinVar RCV001068619, ESP rs370553755, REVEL 0.52, CADD 23.60, Uncertain significance, Familial sleep-related hypermotor epilepsy
- A34V (p.Ala34Val), Ensembl rs2068775206, REVEL 0.32, CADD 21.10
- H35D (p.His35Asp), TOPMed rs1172993847
- H35Q (p.His35Gln), NCI-TCGA TCGA novel, REVEL 0.33, CADD 2.52, Variant assessed as somatic; moderate impact.
- A36D (p.Ala36Asp), rs2068775011, ClinGen CA409643902, ClinVar RCV001945682, TOPMed rs2068775011, AlphaMissense 0.57, MetaLR 0.31, Uncertain significance, Familial sleep-related hypermotor epilepsy
- A36T (p.Ala36Thr), NCI-TCGA Cosmic COSV1009, REVEL 0.43, CADD 22.10, Variant assessed as somatic; moderate impact.
- E37K (p.Glu37Lys), rs778087682, ClinGen CA9957969, NCI-TCGA Cosmic COSV6471, ClinVar RCV001351324, REVEL 0.52, AlphaMissense 0.76, Uncertain significance, Familial sleep-related hypermotor epilepsy
- E37Q (p.Glu37Gln), rs778087682, ClinGen CA409643886, ClinVar RCV002795351, ClinVar RCV005535423, AlphaMissense 0.76, MetaLR 0.46, Uncertain significance, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases
- E37V (p.Glu37Val), NCI-TCGA Cosmic COSV6471, REVEL 0.64, CADD 26.40, Variant assessed as somatic; moderate impact.
- E38D (p.Glu38Asp), gnomAD rs1165591521, REVEL 0.11, CADD 17.90
- E38G (p.Glu38Gly), rs756100070, ClinGen CA409643848, ClinVar RCV002180824, ExAC rs756100070, REVEL 0.24, CADD 33.00, Likely benign, Familial sleep-related hypermotor epilepsy
- E38Q (p.Glu38Gln), rs1428100117, ClinGen CA409643859, ClinVar RCV001214676, ClinVar RCV005241436, REVEL 0.17, CADD 25.70, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not provided
- E38V (p.Glu38Val), rs756100070, ClinGen CA9957968, ClinVar RCV001313971, ExAC rs756100070, REVEL 0.33, CADD 31.00, Likely benign, Familial sleep-related hypermotor epilepsy
- R39Q (p.Arg39Gln), rs1412355004, ClinGen CA409643834, ClinVar RCV001354895, ClinVar RCV002547597, REVEL 0.33, CADD 28.00, Uncertain significance, Inborn genetic diseases; Familial sleep-related hypermotor epilepsy
- R39W (p.Arg39Trp), TOPMed rs1405224423, gnomAD rs1405224423, REVEL 0.58, CADD 28.70
- L40F (p.Leu40Phe), rs1568819698, ClinGen CA409643823, ClinVar RCV001230238, ClinVar RCV004774328, REVEL 0.68, CADD 29.30, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- L41P (p.Leu41Pro), gnomAD rs1179302282
- F45L (p.Phe45Leu), rs766240756, NCI-TCGA TCGA novel, ClinGen CA409643743, ClinVar RCV001230824, REVEL 0.31, CADD 25.30, Uncertain significance, Familial sleep-related hypermotor epilepsy
- S46F (p.Ser46Phe), NCI-TCGA Cosmic COSV6471, REVEL 0.17, CADD 26.00, Variant assessed as somatic; moderate impact.
- S46P (p.Ser46Pro), TOPMed rs1429009238, gnomAD rs1429009238, REVEL 0.24, CADD 25.40
- G47D (p.Gly47Asp), rs764990637, ClinGen CA16608414, ClinVar RCV000419664, ExAC rs764990637, REVEL 0.21, CADD 21.50, Uncertain significance, not provided
- G47S (p.Gly47Ser), rs750423296, ClinGen CA9957964, ClinVar RCV003747624, ExAC rs750423296, REVEL 0.11, CADD 22.50, Uncertain significance, Familial sleep-related hypermotor epilepsy
- G47V (p.Gly47Val), ExAC rs764990637, TOPMed rs764990637, gnomAD rs764990637, REVEL 0.41, CADD 24.80, Uncertain significance
- Y48* (p.Tyr48Ter), ExAC rs199636959, gnomAD rs199636959
- N49D (p.Asn49Asp), TOPMed rs2068773820, REVEL 0.39, CADD 27.70
- N49K (p.Asn49Lys), rs201484306, TOPMed rs201484306, gnomAD rs201484306, ClinGen CA409643650, REVEL 0.61, CADD 25.20, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- K50N (p.Lys50Asn), TOPMed rs985967668, gnomAD rs985967668, Likely benign
- W51* (p.Trp51Ter), rs2516573282, ClinGen CA409643590, ClinVar RCV003012345, Uncertain significance
- W51R (p.Trp51Arg), TOPMed rs1350122328
- S52F (p.Ser52Phe), Ensembl rs2068773527
- S52P (p.Ser52Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R53* (p.Arg53Ter), TOPMed rs2054226040, CADD 40.00
- R53L (p.Arg53Leu), TOPMed rs1286318558, gnomAD rs1286318558, REVEL 0.73, CADD 28.30, Uncertain significance, Familial sleep-related hypermotor epilepsy
- R53Q (p.Arg53Gln), rs1286318558, ClinGen CA409643548, NCI-TCGA Cosmic COSV6471, ClinVar RCV001887297, REVEL 0.69, CADD 28.70, Uncertain significance, Familial sleep-related hypermotor epilepsy
- P54R (p.Pro54Arg), rs2145408375, ClinGen CA409643530, ClinVar RCV002037059, Ensembl rs2145408375, AlphaMissense 0.99, MetaLR 0.96, Uncertain significance, Familial sleep-related hypermotor epilepsy
- P54S (p.Pro54Ser), TOPMed rs1363018977, gnomAD rs1363018977
- V55M (p.Val55Met), rs1349610263, ClinGen CA409643508, NCI-TCGA Cosmic COSV6471, ClinVar RCV001310034, REVEL 0.53, CADD 26.10, Uncertain significance, Familial sleep-related hypermotor epilepsy
- A56P (p.Ala56Pro), ExAC rs763826732, gnomAD rs763826732, REVEL 0.03, CADD 21.90
- A56S (p.Ala56Ser), NCI-TCGA Cosmic COSV6471, Variant assessed as somatic; moderate impact.
- A56V (p.Ala56Val), NCI-TCGA Cosmic COSV6471, Uncertain significance, Familial sleep-related hypermotor epilepsy
- N57D (p.Asn57Asp), Ensembl rs200553253
- N57S (p.Asn57Ser), rs2145408343, ClinGen CA409643444, ClinVar RCV002214235, ClinVar RCV006470234, AlphaMissense 0.12, MetaLR 0.22, Uncertain significance, not provided; Familial sleep-related hypermotor epilepsy
- N57T (p.Asn57Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- I58M (p.Ile58Met), rs2068772907, ClinGen CA409643419, ClinVar RCV001341800, Ensembl rs2068772907, AlphaMissense 0.13, MetaLR 0.06, Uncertain significance, Familial sleep-related hypermotor epilepsy
- I58V (p.Ile58Val), rs760044129, ClinGen CA9957958, ClinVar RCV001342112, ExAC rs760044129, REVEL 0.08, CADD 17.90, Uncertain significance, Familial sleep-related hypermotor epilepsy
- S59L (p.Ser59Leu), rs775143571, ClinGen CA9957957, ClinVar RCV000700450, ClinVar RCV002510964, REVEL 0.40, CADD 26.10, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- D60E (p.Asp60Glu), rs112051150, ClinGen CA9957954, ClinVar RCV000534619, ExAC rs112051150, REVEL 0.22, CADD 6.63, Uncertain significance, Familial sleep-related hypermotor epilepsy
- D60N (p.Asp60Asn), TOPMed rs1882771189
- V61L (p.Val61Leu), rs150451372, ClinGen CA317445954, ClinVar RCV000654305, ESP rs150451372, REVEL 0.03, CADD 19.50, Uncertain significance, Familial sleep-related hypermotor epilepsy
- V61M (p.Val61Met), rs150451372, ClinGen CA9957953, ClinVar RCV001928271, ESP rs150451372, REVEL 0.09, CADD 22.80, Uncertain significance, Familial sleep-related hypermotor epilepsy
- V62I (p.Val62Ile), rs2516573166, ClinGen CA409643339, ClinVar RCV003747101, Uncertain significance, Familial sleep-related hypermotor epilepsy
- V64D (p.Val64Asp), Ensembl rs1346127345
- V64I (p.Val64Ile), rs756367182, ClinGen CA9957951, ClinVar RCV002009834, ClinVar RCV002573510, REVEL 0.52, CADD 22.50, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases; not provide
- V64L (p.Val64Leu), ExAC rs756367182, TOPMed rs756367182, gnomAD rs756367182, Uncertain significance
- R65C (p.Arg65Cys), rs748440038, ClinGen CA9957950, ClinVar RCV000654303, ExAC rs748440038, REVEL 0.45, CADD 23.80, Uncertain significance, Familial sleep-related hypermotor epilepsy
- R65H (p.Arg65His), rs200867143, ClinGen CA9957949, ClinVar RCV001060724, 1000Genomes rs200867143, REVEL 0.14, CADD 15.70, Likely benign, Familial sleep-related hypermotor epilepsy
- F66L (p.Phe66Leu), rs201018244, TOPMed rs201018244, gnomAD rs201018244, ClinGen CA317445927, REVEL 0.49, CADD 17.40, Uncertain significance, Familial sleep-related hypermotor epilepsy; Autosomal dominant nocturnal frontal
- G67D (p.Gly67Asp), rs1568819500, ClinGen CA409643220, ClinVar RCV001862058, ClinVar RCV002318619, AlphaMissense 0.89, MetaLR 0.55, Uncertain significance, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases
- G67R (p.Gly67Arg), ExAC rs750325388, TOPMed rs750325388, gnomAD rs750325388, REVEL 0.71, CADD 25.60, Likely benign
- G67S (p.Gly67Ser), rs750325388, ClinGen CA9957945, ClinVar RCV000762353, ClinVar RCV002533903, REVEL 0.63, CADD 25.80, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not provided
- L68V (p.Leu68Val), Ensembl rs2068771710, REVEL 0.45, CADD 18.90, Uncertain significance, Familial sleep-related hypermotor epilepsy
- S69C (p.Ser69Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A71T (p.Ala71Thr), rs200527878, ClinGen CA9957943, ClinVar RCV000549537, 1000Genomes rs200527878, REVEL 0.49, CADD 23.70, Likely benign, Familial sleep-related hypermotor epilepsy
- A71V (p.Ala71Val), rs753677594, ClinGen CA9957942, ClinVar RCV000498928, ClinVar RCV001053897, REVEL 0.70, CADD 25.80, Uncertain significance, Familial sleep-related hypermotor epilepsy; not provided
- Q72E (p.Gln72Glu), NCI-TCGA TCGA novel, REVEL 0.79, CADD 24.90, Variant assessed as somatic; moderate impact.
- I74L (p.Ile74Leu), rs2068771449, ClinGen CA409643071, ClinVar RCV001049783, ClinVar RCV002553211, REVEL 0.52, CADD 25.00, Uncertain significance, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases
- D75E (p.Asp75Glu), NCI-TCGA Cosmic COSV6471, Variant assessed as somatic; moderate impact.
- D75N (p.Asp75Asn), TOPMed rs930512598, gnomAD rs930512598, REVEL 0.40, CADD 23.10
- V76G (p.Val76Gly), rs1285263254, ClinGen CA409643037, ClinVar RCV003747031, TOPMed rs1285263254, REVEL 0.95, CADD 32.00, Uncertain significance, Familial sleep-related hypermotor epilepsy
- V76M (p.Val76Met), rs201115841, ClinGen CA9957940, ClinVar RCV001223917, ClinVar RCV003222263, REVEL 0.78, CADD 27.20, Uncertain significance, not provided; Familial sleep-related hypermotor epilepsy
- D77A (p.Asp77Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D77N (p.Asp77Asn), rs1204737071, ClinGen CA409641533, ClinVar RCV000691999, TOPMed rs1204737071, REVEL 0.47, CADD 25.30, Uncertain significance, Familial sleep-related hypermotor epilepsy
- E78K (p.Glu78Lys), Ensembl rs2145402100, REVEL 0.91, CADD 25.00
- K79N (p.Lys79Asn), ExAC rs747023127, gnomAD rs747023127, REVEL 0.74, CADD 25.60, Likely benign
- K79R (p.Lys79Arg), ExAC rs768877090, gnomAD rs768877090, REVEL 0.64, CADD 24.30
- N80K (p.Asn80Lys), rs2516563968, ClinGen CA409641504, ClinVar RCV003397747, REVEL 0.74, CADD 25.10, Uncertain significance, CHRNA4-related disorder
- N80S (p.Asn80Ser), ExAC rs780176022, gnomAD rs780176022, REVEL 0.59, CADD 24.20
- Q81H (p.Gln81His), Ensembl rs1601489847, REVEL 0.76, CADD 25.50
- M82T (p.Met82Thr), rs2068719750, ClinGen CA409641490, ClinVar RCV001265534, ClinVar RCV006250995, AlphaMissense 0.78, MetaLR 0.19, Uncertain significance, Autosomal dominant nocturnal frontal lobe epilepsy 1; not provided
- M83V (p.Met83Val), ExAC rs772099807, gnomAD rs772099807, REVEL 0.89, CADD 26.60
- T84S (p.Thr84Ser), gnomAD rs1341495482, REVEL 0.75, CADD 25.40
- T85M (p.Thr85Met), rs199699339, ClinGen CA9957908, ClinVar RCV000444554, ClinVar RCV000654309, REVEL 0.85, CADD 25.90, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; not provided
- T85R (p.Thr85Arg), ExAC rs199699339, TOPMed rs199699339, gnomAD rs199699339, REVEL 0.92, CADD 25.10, Likely benign
- N86D (p.Asn86Asp), Ensembl rs1021423232, REVEL 0.86, CADD 27.40
- N86K (p.Asn86Lys), rs140239470, ClinGen CA409641461, ClinVar RCV001568770, 1000Genomes rs140239470, REVEL 0.57, CADD 19.90, Uncertain significance, not provided
- N86S (p.Asn86Ser), TOPMed rs2068719482, gnomAD rs2068719482, REVEL 0.79, CADD 25.80
- V87I (p.Val87Ile), ExAC rs780927117, TOPMed rs780927117, gnomAD rs780927117, REVEL 0.56, CADD 23.60, Uncertain significance
- V87L (p.Val87Leu), rs780927117, ClinGen CA409641458, ClinVar RCV002437129, ExAC rs780927117, REVEL 0.49, CADD 21.90, Uncertain significance, Inborn genetic diseases
- W88* (p.Trp88Ter), rs2145401994, ClinGen CA409641446, ClinVar RCV002048254, Ensembl rs2145401994, CADD 37.00, Uncertain significance
- K90E (p.Lys90Glu), TOPMed rs1430736446
- Q91P (p.Gln91Pro), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- E92Q (p.Glu92Gln), rs146651027, ClinGen CA313605, ClinVar RCV000186963, ClinVar RCV000477750, REVEL 0.64, CADD 28.60, Conflicting interpretations, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases; Autosomal d
- W93L (p.Trp93Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H94N (p.His94Asn), Ensembl rs2145401047
- H94Q (p.His94Gln), ExAC rs754402670, TOPMed rs754402670, gnomAD rs754402670, REVEL 0.23, CADD 5.47, Likely benign
- D95H (p.Asp95His), TOPMed rs761317422, Uncertain significance
- D95N (p.Asp95Asn), rs761317422, ClinGen CA313607, NCI-TCGA Cosmic COSV6471, ClinVar RCV000186964, REVEL 0.88, CADD 27.80, Uncertain significance, not provided
- K97N (p.Lys97Asn), Ensembl rs200089220
- K97R (p.Lys97Arg), ExAC rs764421351, gnomAD rs764421351, REVEL 0.57, CADD 23.90, Uncertain significance, Familial sleep-related hypermotor epilepsy
- L98M (p.Leu98Met), Ensembl rs202055640
- R99C (p.Arg99Cys), rs201160663, ClinGen CA9957875, ClinVar RCV003746847, ExAC rs201160663, REVEL 0.64, CADD 25.60, Uncertain significance, Familial sleep-related hypermotor epilepsy
- R99H (p.Arg99His), rs143103435, ClinGen CA313609, ClinVar RCV000460546, ClinVar RCV000844908, REVEL 0.46, CADD 23.60, Benign/Likely benign, Familial sleep-related hypermotor epilepsy; Inborn genetic diseases; not provide
- W100* (p.Trp100Ter), Ensembl rs2145400990
- W100C (p.Trp100Cys), TOPMed rs2068712709, Uncertain significance, not provided
- D101G (p.Asp101Gly), Ensembl rs2068712598
- D101N (p.Asp101Asn), rs1427242612, ClinGen CA409641349, ClinVar RCV000794716, TOPMed rs1427242612, REVEL 0.12, CADD 19.00, Uncertain significance, Familial sleep-related hypermotor epilepsy
- P102L (p.Pro102Leu), rs759593635, ClinGen CA9957873, ClinVar RCV001325675, ExAC rs759593635, REVEL 0.72, CADD 28.70, Uncertain significance, Familial sleep-related hypermotor epilepsy
- P102Q (p.Pro102Gln), ExAC rs759593635, TOPMed rs759593635, gnomAD rs759593635, Uncertain significance
- P102T (p.Pro102Thr), Ensembl rs2145400974
- A103T (p.Ala103Thr), rs1389368921, gnomAD rs1389368921, AlphaMissense 0.07, MetaLR 0.21, Variant assessed as somatic; moderate impact.
- D104A (p.Asp104Ala), rs202042826, ClinGen CA317441862, ClinVar RCV001206006, ClinVar RCV001587223, REVEL 0.70, CADD 26.30, Conflicting interpretations, not provided; Familial sleep-related hypermotor epilepsy; Inborn genetic disease
- Y105C (p.Tyr105Cys), rs771191068, ExAC rs771191068, gnomAD rs771191068, MetaLR 0.72, MetaSVM 0.46, Variant assessed as somatic; moderate impact.
- Y105F (p.Tyr105Phe), ExAC rs771191068, gnomAD rs771191068, REVEL 0.56, MetaLR 0.72
- N107S (p.Asn107Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T109A (p.Thr109Ala), rs145017594, ClinGen CA9957869, ClinVar RCV002467070, ClinVar RCV005098435, REVEL 0.50, CADD 22.10, Uncertain significance, not provided; Familial sleep-related hypermotor epilepsy; not specified
Public CHRNA4 analysis runs
- CHRNA4 analysis run — CHRNA4 (1,393 variants) — completed 2026-08-21