20-63346483-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.*255C>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 0.000707 in 656,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 1 hom. )
Consequence
CHRNA4
NM_000744.7 3_prime_UTR
NM_000744.7 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.26
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=-0.93).
BP6
Variant 20-63346483-G-A is Benign according to our data. Variant chr20-63346483-G-A is described in ClinVar as [Benign]. Clinvar id is 1269727.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 318 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.*255C>T | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000370263.9 | NP_000735.1 | ||
CHRNA4 | NR_046317.2 | n.2348C>T | non_coding_transcript_exon_variant | Exon 6 of 6 | ||||
CHRNA4 | NM_001256573.2 | c.*255C>T | 3_prime_UTR_variant | Exon 6 of 6 | NP_001243502.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00208 AC: 317AN: 152148Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
317
AN:
152148
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
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AF:
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000398 AC: 52AN: 130568 AF XY: 0.000295 show subpopulations
GnomAD2 exomes
AF:
AC:
52
AN:
130568
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.000290 AC: 146AN: 503734Hom.: 1 Cov.: 4 AF XY: 0.000219 AC XY: 60AN XY: 273588 show subpopulations
GnomAD4 exome
AF:
AC:
146
AN:
503734
Hom.:
Cov.:
4
AF XY:
AC XY:
60
AN XY:
273588
show subpopulations
African (AFR)
AF:
AC:
102
AN:
14746
American (AMR)
AF:
AC:
11
AN:
33000
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
18568
East Asian (EAS)
AF:
AC:
4
AN:
28152
South Asian (SAS)
AF:
AC:
2
AN:
61478
European-Finnish (FIN)
AF:
AC:
0
AN:
28272
Middle Eastern (MID)
AF:
AC:
0
AN:
2234
European-Non Finnish (NFE)
AF:
AC:
9
AN:
289808
Other (OTH)
AF:
AC:
17
AN:
27476
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
10
20
30
40
50
0.00
0.20
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0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00209 AC: 318AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.00187 AC XY: 139AN XY: 74446 show subpopulations
GnomAD4 genome
AF:
AC:
318
AN:
152266
Hom.:
Cov.:
33
AF XY:
AC XY:
139
AN XY:
74446
show subpopulations
African (AFR)
AF:
AC:
299
AN:
41542
American (AMR)
AF:
AC:
13
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
2
AN:
5178
South Asian (SAS)
AF:
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68020
Other (OTH)
AF:
AC:
3
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
16
33
49
66
82
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: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
May 30, 2020
GeneDx
Significance: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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