rs755204

Positions:

• chr20-63362813-G-A

Variant summary

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

The NR_110634.1(LOC100130587):​n.306+872G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,240 control chromosomes in the GnomAD database, including 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 0.086 (563 hom., cov: 33)
• Consequence: LOC100130587 NR_110634.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100130587	NR_110634.1	n.306+872G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000370257.1	n.306+872G>A		intron_variant, non_coding_transcript_variant		2
CHRNA4	ENST00000463705.5	n.1031+11068C>T		intron_variant, non_coding_transcript_variant		1
CHRNA4	ENST00000675470.1	c.-964-295C>T		intron_variant				ENSP00000502096

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13130 AN: 152122 Hom.: 564 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0863 AC: 13138 AN: 152240 Hom.: 563 Cov.: 33 AF XY: 0.0871 AC XY: 6481 AN XY: 74430

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0757

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.0875

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0734 Hom.: 146

Bravo AF: 0.0861

Asia WGS AF: 0.107 AC: 372 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	5.1
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs755204; hg19: chr20-61994165;