20-63358042-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000744.7(CHRNA4):​c.228+1506A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 152,140 control chromosomes in the GnomAD database, including 806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 806 hom., cov: 33)

Consequence

CHRNA4
NM_000744.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHRNA4NM_000744.7 linkuse as main transcriptc.228+1506A>G intron_variant ENST00000370263.9 NP_000735.1 P43681-1B4DK78Q59FV0
CHRNA4NM_001256573.2 linkuse as main transcriptc.-319+1506A>G intron_variant NP_001243502.1 P43681Q4VAQ3B4DK78Q59FV0
CHRNA4NR_046317.2 linkuse as main transcriptn.412+1506A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHRNA4ENST00000370263.9 linkuse as main transcriptc.228+1506A>G intron_variant 1 NM_000744.7 ENSP00000359285.4 P43681-1

Frequencies

GnomAD3 genomes
AF:
0.0982
AC:
14936
AN:
152022
Hom.:
804
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.141
Gnomad AMI
AF:
0.0813
Gnomad AMR
AF:
0.0774
Gnomad ASJ
AF:
0.0888
Gnomad EAS
AF:
0.130
Gnomad SAS
AF:
0.166
Gnomad FIN
AF:
0.0871
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.0715
Gnomad OTH
AF:
0.106
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0984
AC:
14966
AN:
152140
Hom.:
806
Cov.:
33
AF XY:
0.0994
AC XY:
7390
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.141
Gnomad4 AMR
AF:
0.0774
Gnomad4 ASJ
AF:
0.0888
Gnomad4 EAS
AF:
0.130
Gnomad4 SAS
AF:
0.166
Gnomad4 FIN
AF:
0.0871
Gnomad4 NFE
AF:
0.0715
Gnomad4 OTH
AF:
0.104
Alfa
AF:
0.0306
Hom.:
23
Bravo
AF:
0.0970
Asia WGS
AF:
0.149
AC:
517
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
11
DANN
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3787141; hg19: chr20-61989394; API