20-63346719-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000744.7(CHRNA4):c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,599,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CHRNA4
NM_000744.7 3_prime_UTR
NM_000744.7 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.22
Publications
0 publications found
Genes affected
CHRNA4 (HGNC:1958): (cholinergic receptor nicotinic alpha 4 subunit) This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
CHRNA4 Gene-Disease associations (from GenCC):
- autosomal dominant nocturnal frontal lobe epilepsy 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- familial sleep-related hypermotor epilepsyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal dominant nocturnal frontal lobe epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 20-63346719-G-A is Benign according to our data. Variant chr20-63346719-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1283389.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.*19C>T | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000370263.9 | NP_000735.1 | ||
CHRNA4 | NR_046317.2 | n.2112C>T | non_coding_transcript_exon_variant | Exon 6 of 6 | ||||
CHRNA4 | NM_001256573.2 | c.*19C>T | 3_prime_UTR_variant | Exon 6 of 6 | NP_001243502.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
5
AN:
152230
Hom.:
Cov.:
33
Gnomad AFR
AF:
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GnomAD2 exomes AF: 0.0000264 AC: 6AN: 227152 AF XY: 0.0000321 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
227152
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.0000117 AC: 17AN: 1447674Hom.: 0 Cov.: 32 AF XY: 0.0000153 AC XY: 11AN XY: 720100 show subpopulations
GnomAD4 exome
AF:
AC:
17
AN:
1447674
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
720100
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33300
American (AMR)
AF:
AC:
0
AN:
43522
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26000
East Asian (EAS)
AF:
AC:
2
AN:
39330
South Asian (SAS)
AF:
AC:
2
AN:
85666
European-Finnish (FIN)
AF:
AC:
0
AN:
45358
Middle Eastern (MID)
AF:
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1108718
Other (OTH)
AF:
AC:
2
AN:
60060
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74366 show subpopulations
GnomAD4 genome
AF:
AC:
5
AN:
152230
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
74366
show subpopulations
African (AFR)
AF:
AC:
3
AN:
41464
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68040
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Feb 01, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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