4-46250049-C-T

Variant summary

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

The NM_000807.4(GABRA2):c.*259G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 356,358 control chromosomes in the GnomAD database, including 67,838 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 0.63 (30291 hom., cov: 31)
  • Exomes 𝑓: 0.60 (37547 hom.)
• Consequence: GABRA2 NM_000807.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.*259G>A		3_prime_UTR_variant	10/10	ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.*259G>A		3_prime_UTR_variant	10/10	1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94668 AN: 151176 Hom.: 30273 Cov.: 31

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.600 AC: 122986 AN: 205062 Hom.: 37547 Cov.: 2 AF XY: 0.605 AC XY: 64175 AN XY: 106060

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.626 AC: 94726 AN: 151296 Hom.: 30291 Cov.: 31 AF XY: 0.627 AC XY: 46318 AN XY: 73918

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.630

Alfa AF: 0.581 Hom.: 11294

Bravo AF: 0.621

Asia WGS AF: 0.652 AC: 2267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.072
Dann	Benign	0.41

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: rs573400; hg19: chr4-46252066;