rs279863

chr4-46311005-C-A

Variant summary

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

The NM_000807.4(GABRA2):c.477-750G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,848 control chromosomes in the GnomAD database, including 11,558 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 0.38 (11558 hom., cov: 33)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.477-750G>T		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.477-750G>T		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57417 AN: 151732 Hom.: 11543 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.378 AC: 57449 AN: 151848 Hom.: 11558 Cov.: 33 AF XY: 0.379 AC XY: 28105 AN XY: 74200

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.372

Alfa AF: 0.415 Hom.: 2737

Bravo AF: 0.382

Asia WGS AF: 0.369 AC: 1278 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.8
Dann	Benign	0.74

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: rs279863; hg19: chr4-46313022;