rs282117

chr6-89271694-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002043.5(GABRR2):c.249A>G(p.Val83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,610,554 control chromosomes in the GnomAD database, including 304,709 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 0.65 (33103 hom., cov: 31)
  • Exomes 𝑓: 0.61 (271606 hom.)
• Consequence: GABRR2 NM_002043.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-0.114 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR2	NM_002043.5	c.249A>G	p.Val83=	synonymous_variant	3/9	ENST00000402938.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR2	ENST00000402938.4	c.249A>G	p.Val83=	synonymous_variant	3/9	1	NM_002043.5	P1
GABRR2	ENST00000602808.1	n.383A>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99489 AN: 151936 Hom.: 33053 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.622 AC: 153083 AN: 245940 Hom.: 48108 AF XY: 0.622 AC XY: 82716 AN XY: 133078

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.590

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.695

Gnomad SAS exome AF: 0.675

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.608 AC: 887318 AN: 1458500 Hom.: 271606 Cov.: 44 AF XY: 0.609 AC XY: 441468 AN XY: 725248

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.705

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.596

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.655 AC: 99591 AN: 152054 Hom.: 33103 Cov.: 31 AF XY: 0.656 AC XY: 48762 AN XY: 74332

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.658

Alfa AF: 0.605 Hom.: 34899

Bravo AF: 0.657

Asia WGS AF: 0.718 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	10
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs282117; hg19: chr6-89981413; COSMIC: COSV68764911; COSMIC: COSV68764911;