rs572227

chr4-46249376-T-C

Variant summary

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

The NM_000807.4(GABRA2):c.*932A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 150,866 control chromosomes in the GnomAD database, including 29,832 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 0.62 (29832 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: GABRA2 NM_000807.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.91).
• 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.*932A>G		3_prime_UTR_variant	10/10	ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.*932A>G		3_prime_UTR_variant	10/10	1	NM_000807.4	P2
GABRA2	ENST00000510861.5	c.*932A>G		3_prime_UTR_variant	10/10	5		P2
GABRA2	ENST00000514090.5	c.*932A>G		3_prime_UTR_variant	10/10	5		P2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 93871 AN: 150748 Hom.: 29817 Cov.: 30

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.623

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.623 AC: 93926 AN: 150866 Hom.: 29832 Cov.: 30 AF XY: 0.623 AC XY: 45889 AN XY: 73668

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.551

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: 0.624

Alfa AF: 0.596 Hom.: 12485

Bravo AF: 0.617

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.059
Dann	Benign	0.51

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: rs572227; hg19: chr4-46251393;