6-89264344-T-C

Position:

• chr6-89264344-T-C

Variant summary

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

The ENST00000402938.4(GABRR2):​c.1086+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,507,348 control chromosomes in the GnomAD database, including 555,347 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 0.84 (53758 hom., cov: 30)
  • Exomes 𝑓: 0.86 (501589 hom.)
• Consequence: GABRR2 ENST00000402938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.1086+68A>G		intron_variant		ENST00000402938.4	NP_002034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.1086+68A>G		intron_variant		1	NM_002043.5	ENSP00000386029	P1
GABRR2	ENST00000602432.1	n.917+68A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127548 AN: 151934 Hom.: 53723 Cov.: 30

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.855

GnomAD4 exome AF: 0.859 AC: 1164786 AN: 1355296 Hom.: 501589 AF XY: 0.859 AC XY: 572465 AN XY: 666812

Gnomad4 AFR exome AF: 0.819

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.806

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.873

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.839 AC: 127634 AN: 152052 Hom.: 53758 Cov.: 30 AF XY: 0.837 AC XY: 62221 AN XY: 74318

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.856

Alfa AF: 0.861 Hom.: 69589

Bravo AF: 0.834

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.19

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: rs723041; hg19: chr6-89974063; COSMIC: COSV68766363;