4-46261847-T-A

Position:

• chr4-46261847-T-A

Variant summary

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

The ENST00000515082.5(GABRA2):​c.*34A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,218,320 control chromosomes in the GnomAD database, including 200,079 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 0.50 (20146 hom., cov: 31)
  • Exomes 𝑓: 0.58 (179933 hom.)
• Consequence: GABRA2 ENST00000515082.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.1059+79A>T		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.1059+79A>T		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75684 AN: 151300 Hom.: 20146 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.542

GnomAD3 exomes AF: 0.569 AC: 135224 AN: 237840 Hom.: 39613 AF XY: 0.585 AC XY: 75696 AN XY: 129360

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.474

Gnomad ASJ exome AF: 0.688

Gnomad EAS exome AF: 0.533

Gnomad SAS exome AF: 0.762

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.576 AC: 614298 AN: 1066902 Hom.: 179933 Cov.: 14 AF XY: 0.585 AC XY: 320295 AN XY: 547820

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.606

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.500 AC: 75692 AN: 151418 Hom.: 20146 Cov.: 31 AF XY: 0.503 AC XY: 37215 AN XY: 73936

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.544

Alfa AF: 0.497 Hom.: 2830

Bravo AF: 0.481

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.69

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: rs10938435; hg19: chr4-46263864;