chr6-89291052-C-T

Variant names:

• chr6-89291052-C-T
• rs6454750
• NM_002043.5:c.220+8707G>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.220+8707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,942 control chromosomes in the GnomAD database, including 15,711 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 0.45 (15711 hom., cov: 31)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 1 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 (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.220+8707G>A		intron_variant	Intron 2 of 8	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.295+8707G>A		intron_variant	Intron 2 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.220+8707G>A		intron_variant	Intron 2 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.354+8707G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68673 AN: 151824 Hom.: 15695 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.452 AC: 68737 AN: 151942 Hom.: 15711 Cov.: 31 AF XY: 0.451 AC XY: 33521 AN XY: 74278

African (AFR) AF: 0.394 AC: 16303 AN: 41378

American (AMR) AF: 0.552 AC: 8430 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3464

East Asian (EAS) AF: 0.477 AC: 2460 AN: 5160

South Asian (SAS) AF: 0.383 AC: 1843 AN: 4818

European-Finnish (FIN) AF: 0.449 AC: 4752 AN: 10584

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31359 AN: 67946

Other (OTH) AF: 0.507 AC: 1067 AN: 2104

Alfa AF: 0.459 Hom.: 5470

Bravo AF: 0.465

Asia WGS AF: 0.403 AC: 1401 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	3.9
DANN	Benign	0.69
PhyloP100		1.4
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: rs6454750; hg19: chr6-90000771;