rs3811995

Variant names:

• chr5-161685687-C-T
• rs3811995
• ENST00000518888.1:n.293-12C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000518888.1(GABRA6):​n.293-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 508,884 control chromosomes in the GnomAD database, including 65,853 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 0.48 (18002 hom., cov: 31)
  • Exomes 𝑓: 0.51 (47851 hom.)
• Consequence: GABRA6 ENST00000518888.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 9 publications found

Genes affected

GABRA6 (HGNC:4080): (gamma-aminobutyric acid type A receptor subunit alpha6) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA6	NM_000811.3	c.-303C>T		upstream_gene_variant		ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000518888.1	n.293-12C>T		intron_variant	Intron 3 of 3	4
GABRA6	ENST00000522269.5	n.352-543C>T		intron_variant	Intron 4 of 6	4
GABRA6	ENST00000274545.10	c.-303C>T		upstream_gene_variant		1	NM_000811.3	ENSP00000274545.5
GABRA6	ENST00000523217.5	c.-303C>T		upstream_gene_variant		5		ENSP00000430527.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72420 AN: 151854 Hom.: 18001 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.509 AC: 181763 AN: 356912 Hom.: 47851 Cov.: 0 AF XY: 0.506 AC XY: 95840 AN XY: 189510

African (AFR) AF: 0.360 AC: 3788 AN: 10522

American (AMR) AF: 0.379 AC: 6092 AN: 16076

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 5577 AN: 10648

East Asian (EAS) AF: 0.308 AC: 7090 AN: 23044

South Asian (SAS) AF: 0.425 AC: 17684 AN: 41650

European-Finnish (FIN) AF: 0.535 AC: 10768 AN: 20116

Middle Eastern (MID) AF: 0.481 AC: 751 AN: 1562

European-Non Finnish (NFE) AF: 0.563 AC: 119713 AN: 212750

Other (OTH) AF: 0.501 AC: 10300 AN: 20544

GnomAD4 genome AF: 0.477 AC: 72429 AN: 151972 Hom.: 18002 Cov.: 31 AF XY: 0.474 AC XY: 35226 AN XY: 74284

African (AFR) AF: 0.356 AC: 14774 AN: 41448

American (AMR) AF: 0.425 AC: 6492 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1828 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1582 AN: 5172

South Asian (SAS) AF: 0.413 AC: 1989 AN: 4816

European-Finnish (FIN) AF: 0.552 AC: 5823 AN: 10558

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38464 AN: 67928

Other (OTH) AF: 0.449 AC: 947 AN: 2108

Alfa AF: 0.528 Hom.: 27508

Bravo AF: 0.458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		1.1
PromoterAI		-0.032	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3811995; hg19: chr5-161112693; COSMIC: COSV50878712; COSMIC: COSV50878712;