rs3787138

Positions:

• chr20-63347872-G-A
• chr20-63347872-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000744.7(CHRNA4):​c.1759-1009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,162 control chromosomes in the GnomAD database, including 47,563 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 0.78 (47563 hom., cov: 33)
• Consequence: CHRNA4 NM_000744.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA4	NM_000744.7	c.1759-1009C>T		intron_variant		ENST00000370263.9	NP_000735.1
CHRNA4	NM_001256573.2	c.1231-1009C>T		intron_variant			NP_001243502.1
CHRNA4	NR_046317.2	n.1968-1009C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA4	ENST00000370263.9	c.1759-1009C>T		intron_variant		1	NM_000744.7	ENSP00000359285.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118135 AN: 152044 Hom.: 47544 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.777 AC: 118200 AN: 152162 Hom.: 47563 Cov.: 33 AF XY: 0.782 AC XY: 58157 AN XY: 74406

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.782

Alfa AF: 0.850 Hom.: 42951

Bravo AF: 0.765

Asia WGS AF: 0.816 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs3787138; hg19: chr20-61979224; COSMIC: COSV64721263; COSMIC: COSV64721263;