rs9451191

Variant names:

• chr6-89263393-G-A
• rs9451191
• NM_002043.5:c.1086+1019C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002043.5(GABRR2):​c.1086+1019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,110 control chromosomes in the GnomAD database, including 3,460 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 0.20 (3460 hom., cov: 33)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.1086+1019C>T		intron_variant	Intron 8 of 8	ENST00000402938.4	NP_002034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.1086+1019C>T		intron_variant	Intron 8 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602432.1	n.917+1019C>T		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30867 AN: 151992 Hom.: 3460 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.203 AC: 30886 AN: 152110 Hom.: 3460 Cov.: 33 AF XY: 0.202 AC XY: 15010 AN XY: 74336

African (AFR) AF: 0.132 AC: 5495 AN: 41496

American (AMR) AF: 0.185 AC: 2821 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3472

East Asian (EAS) AF: 0.0449 AC: 233 AN: 5188

South Asian (SAS) AF: 0.186 AC: 896 AN: 4824

European-Finnish (FIN) AF: 0.264 AC: 2789 AN: 10552

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17183 AN: 67974

Other (OTH) AF: 0.219 AC: 463 AN: 2110

Alfa AF: 0.239 Hom.: 3697

Bravo AF: 0.193

Asia WGS AF: 0.135 AC: 469 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	4.0
DANN	Benign	0.63
PhyloP100		0.36
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: rs9451191; hg19: chr6-89973112;