NM_002043.5:c.890-251T>C

Variant names:

• chr6-89264859-A-G
• rs9294426
• NM_002043.5:c.890-251T>C

Variant summary

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

The NM_002043.5(GABRR2):​c.890-251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 151,998 control chromosomes in the GnomAD database, including 37,026 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 0.70 (37026 hom., cov: 31)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.890-251T>C		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.890-251T>C		intron_variant	Intron 7 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602432.1	n.721-251T>C		intron_variant	Intron 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105801 AN: 151880 Hom.: 37004 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.697 AC: 105868 AN: 151998 Hom.: 37026 Cov.: 31 AF XY: 0.699 AC XY: 51900 AN XY: 74300

African (AFR) AF: 0.665 AC: 27593 AN: 41472

American (AMR) AF: 0.674 AC: 10301 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3472

East Asian (EAS) AF: 0.669 AC: 3403 AN: 5086

South Asian (SAS) AF: 0.757 AC: 3654 AN: 4824

European-Finnish (FIN) AF: 0.728 AC: 7710 AN: 10584

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48575 AN: 67964

Other (OTH) AF: 0.708 AC: 1494 AN: 2110

Alfa AF: 0.690 Hom.: 23427

Bravo AF: 0.689

Asia WGS AF: 0.725 AC: 2520 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	6.0
DANN	Benign	0.50
PhyloP100		-0.49
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: rs9294426; hg19: chr6-89974578; COSMIC: COSV68766267;