rs3756007

Positions:

• chr4-46389047-T-C

Variant summary

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

The NM_001114175.3(GABRA2):​c.-341A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 1,076,532 control chromosomes in the GnomAD database, including 2,153 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 0.057 (516 hom., cov: 30)
  • Exomes 𝑓: 0.053 (1637 hom.)
• Consequence: GABRA2 NM_001114175.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.-10-331A>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.-10-331A>G		intron_variant		1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8658 AN: 151608 Hom.: 512 Cov.: 30

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0567

GnomAD4 exome AF: 0.0533 AC: 49248 AN: 924808 Hom.: 1637 Cov.: 34 AF XY: 0.0527 AC XY: 22822 AN XY: 433112

Gnomad4 AFR exome AF: 0.00639

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0972

Gnomad4 NFE exome AF: 0.0521

Gnomad4 OTH exome AF: 0.0646

GnomAD4 genome AF: 0.0571 AC: 8669 AN: 151724 Hom.: 516 Cov.: 30 AF XY: 0.0624 AC XY: 4628 AN XY: 74118

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0465

Gnomad4 OTH AF: 0.0561

Alfa AF: 0.0458 Hom.: 143

Bravo AF: 0.0646

Asia WGS AF: 0.145 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.59

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: rs3756007; hg19: chr4-46391064;