rs189957

chr4-46344662-A-G

Variant summary

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

The NM_000807.4(GABRA2):c.188-11980T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,508 control chromosomes in the GnomAD database, including 16,543 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 0.46 (16543 hom., cov: 31)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.188-11980T>C		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.188-11980T>C		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70317 AN: 151390 Hom.: 16510 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.465 AC: 70395 AN: 151508 Hom.: 16543 Cov.: 31 AF XY: 0.466 AC XY: 34460 AN XY: 73992

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.434

Alfa AF: 0.453 Hom.: 15633

Bravo AF: 0.473

Asia WGS AF: 0.441 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.4
Dann	Benign	0.50

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: rs189957; hg19: chr4-46346679;