rs6454752

Variant names:

• chr6-89308642-C-T
• rs6454752
• NM_002043.5:c.113+6411G>A

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002043.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	NM_002043.5	MANE Select	c.113+6411G>A		intron	N/A	NP_002034.3	P28476-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.113+6411G>A		intron	N/A	ENSP00000386029.4	P28476-1
	GABRR2	ENST00000602808.1	TSL:3	n.247+6411G>A		intron	N/A

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

African (AFR) AF: 0.268 AC: 11119 AN: 41442

American (AMR) AF: 0.234 AC: 3579 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3468

East Asian (EAS) AF: 0.109 AC: 566 AN: 5174

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4816

European-Finnish (FIN) AF: 0.249 AC: 2629 AN: 10558

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15374 AN: 67974

Other (OTH) AF: 0.225 AC: 475 AN: 2108

Alfa AF: 0.229 Hom.: 6866

Bravo AF: 0.238

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.40
PhyloP100		0.17
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: rs6454752; hg19: chr6-90018361;