NM_002043.5:c.113+4805G>A

Variant names:

• chr6-89310248-C-T
• rs9294432
• NM_002043.5:c.113+4805G>A

Variant summary

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

The NM_002043.5(GABRR2):​c.113+4805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,936 control chromosomes in the GnomAD database, including 29,130 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 0.59 (29130 hom., cov: 30)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.113+4805G>A		intron_variant	Intron 1 of 8	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.188+4805G>A		intron_variant	Intron 1 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.113+4805G>A		intron_variant	Intron 1 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.247+4805G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89846 AN: 151818 Hom.: 29070 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.592 AC: 89967 AN: 151936 Hom.: 29130 Cov.: 30 AF XY: 0.595 AC XY: 44184 AN XY: 74248

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.573

Alfa AF: 0.483 Hom.: 17745

Bravo AF: 0.603

Asia WGS AF: 0.758 AC: 2636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.29

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: rs9294432; hg19: chr6-90019967;