rs279841

Positions:

• chr4-46338746-G-A
• chr4-46338746-G-T

Variant summary

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

The NM_000807.4(GABRA2):​c.188-6064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,570 control chromosomes in the GnomAD database, including 11,495 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 (11495 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.188-6064C>T		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.188-6064C>T		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57115 AN: 151452 Hom.: 11480 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.377 AC: 57144 AN: 151570 Hom.: 11495 Cov.: 32 AF XY: 0.379 AC XY: 28046 AN XY: 74044

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.368

Alfa AF: 0.390 Hom.: 6276

Bravo AF: 0.380

Asia WGS AF: 0.402 AC: 1393 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.21

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: rs279841; hg19: chr4-46340763;