4-46337053-T-A

Position:

• chr4-46337053-T-A

Variant summary

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

The NM_000807.4(GABRA2):​c.188-4371A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,976 control chromosomes in the GnomAD database, including 11,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.38 (11828 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.919

Genes affected

GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.188-4371A>T		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.188-4371A>T		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58197 AN: 151858 Hom.: 11814 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.383 AC: 58226 AN: 151976 Hom.: 11828 Cov.: 32 AF XY: 0.385 AC XY: 28606 AN XY: 74264

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.377

Alfa AF: 0.412 Hom.: 1758

Bravo AF: 0.386

Asia WGS AF: 0.406 AC: 1407 AN: 3476

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Alcoholism, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.68

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: rs279836; hg19: chr4-46339070;