rs12206367

Variant names:

• chr6-89264907-C-A
• rs12206367
• NM_002043.5:c.890-299G>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.890-299G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,094 control chromosomes in the GnomAD database, including 764 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 0.090 (764 hom., cov: 31)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.890-299G>T		intron_variant	Intron 7 of 8	ENST00000402938.4	NP_002034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.890-299G>T		intron_variant	Intron 7 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602432.1	n.721-299G>T		intron_variant	Intron 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13620 AN: 151976 Hom.: 763 Cov.: 31

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.00313

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0692

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

GnomAD4 genome AF: 0.0896 AC: 13629 AN: 152094 Hom.: 764 Cov.: 31 AF XY: 0.0902 AC XY: 6701 AN XY: 74314

African (AFR) AF: 0.0601 AC: 2495 AN: 41540

American (AMR) AF: 0.0654 AC: 1000 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3468

East Asian (EAS) AF: 0.00294 AC: 15 AN: 5096

South Asian (SAS) AF: 0.0509 AC: 245 AN: 4818

European-Finnish (FIN) AF: 0.140 AC: 1484 AN: 10564

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7915 AN: 67998

Other (OTH) AF: 0.0685 AC: 145 AN: 2116

Alfa AF: 0.101 Hom.: 1636

Bravo AF: 0.0819

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.67
PhyloP100		-0.80
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: rs12206367; hg19: chr6-89974626;