rs279871

Positions:

• chr4-46303716-T-C

Variant summary

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

The NM_000807.4(GABRA2):​c.704-104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 951,780 control chromosomes in the GnomAD database, including 87,284 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 (11724 hom., cov: 32)
  • Exomes 𝑓: 0.43 (75560 hom.)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -1.83

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.704-104A>G		intron_variant		ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.704-104A>G		intron_variant		1	NM_000807.4	ENSP00000371033	P2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57974 AN: 151964 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.431 AC: 344593 AN: 799698 Hom.: 75560 AF XY: 0.424 AC XY: 172842 AN XY: 408082

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.381 AC: 58008 AN: 152082 Hom.: 11724 Cov.: 32 AF XY: 0.382 AC XY: 28381 AN XY: 74342

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.376

Alfa AF: 0.425 Hom.: 13120

Bravo AF: 0.386

Asia WGS AF: 0.371 AC: 1287 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	-0.93
CADD	Benign	0.071
DANN	Benign	0.38

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: rs279871; hg19: chr4-46305733;