rs6454752

chr6-89308642-C-T

Variant summary

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

The NM_002043.5(GABRR2):c.113+6411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,044 control chromosomes in the GnomAD database, including 4,452 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 0.24 (4452 hom., cov: 31)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR2	NM_002043.5	c.113+6411G>A		intron_variant		ENST00000402938.4
GABRR2	XM_047418599.1	c.188+6411G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR2	ENST00000402938.4	c.113+6411G>A		intron_variant		1	NM_002043.5	P1
GABRR2	ENST00000602808.1	n.247+6411G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36281 AN: 151926 Hom.: 4446 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.239 AC: 36305 AN: 152044 Hom.: 4452 Cov.: 31 AF XY: 0.239 AC XY: 17747 AN XY: 74348

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.225

Alfa AF: 0.229 Hom.: 5318

Bravo AF: 0.238

Asia WGS AF: 0.194 AC: 678 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	2.0
Dann	Benign	0.40

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: rs6454752; hg19: chr6-90018361;