rs2273508

chr6-89268129-C-T

Variant summary

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

The NM_002043.5(GABRR2):c.513-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,536,946 control chromosomes in the GnomAD database, including 14,428 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 0.12 (1290 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13138 hom.)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR2	NM_002043.5	c.513-33G>A		intron_variant		ENST00000402938.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR2	ENST00000402938.4	c.513-33G>A		intron_variant		1	NM_002043.5	P1
GABRR2	ENST00000602432.1	n.344-33G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18436 AN: 152068 Hom.: 1290 Cov.: 33

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.146 AC: 28196 AN: 193676 Hom.: 2606 AF XY: 0.145 AC XY: 14950 AN XY: 102962

Gnomad AFR exome AF: 0.0955

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.0934

Gnomad EAS exome AF: 0.415

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.128 AC: 176608 AN: 1384758 Hom.: 13138 Cov.: 24 AF XY: 0.127 AC XY: 87558 AN XY: 687986

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.0897

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.121 AC: 18434 AN: 152188 Hom.: 1290 Cov.: 33 AF XY: 0.123 AC XY: 9128 AN XY: 74380

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0884

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.132

Alfa AF: 0.120 Hom.: 857

Bravo AF: 0.122

Asia WGS AF: 0.247 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.3
Dann	Benign	0.66

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: rs2273508; hg19: chr6-89977848; COSMIC: COSV68766463; COSMIC: COSV68766463;