6-89268129-C-T

Variant names:

• chr6-89268129-C-T
• rs2273508
• NM_002043.5:c.513-33G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002043.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	NM_002043.5	MANE Select	c.513-33G>A		intron	N/A	NP_002034.3	P28476-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.513-33G>A		intron	N/A	ENSP00000386029.4	P28476-1
	GABRR2	ENST00000602432.1	TSL:2	n.344-33G>A		intron	N/A

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

GnomAD2 exomes AF: 0.146 AC: 28196 AN: 193676 AF XY: 0.145

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 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

African (AFR) AF: 0.0934 AC: 2963 AN: 31734

American (AMR) AF: 0.133 AC: 5163 AN: 38904

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 2262 AN: 25208

East Asian (EAS) AF: 0.418 AC: 15675 AN: 37468

South Asian (SAS) AF: 0.118 AC: 9516 AN: 80588

European-Finnish (FIN) AF: 0.123 AC: 6285 AN: 51272

Middle Eastern (MID) AF: 0.123 AC: 648 AN: 5266

European-Non Finnish (NFE) AF: 0.120 AC: 126538 AN: 1056588

Other (OTH) AF: 0.131 AC: 7558 AN: 57730

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

African (AFR) AF: 0.0919 AC: 3817 AN: 41522

American (AMR) AF: 0.124 AC: 1893 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 307 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2042 AN: 5176

South Asian (SAS) AF: 0.129 AC: 620 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10578

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8157 AN: 67994

Other (OTH) AF: 0.132 AC: 280 AN: 2114

Alfa AF: 0.122 Hom.: 1193

Bravo AF: 0.122

Asia WGS AF: 0.247 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.66
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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