6-89270364-T-C

Position:

• chr6-89270364-T-C

Variant summary

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

The ENST00000402938.4(GABRR2):​c.289-1130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,056 control chromosomes in the GnomAD database, including 33,104 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 0.66 (33093 hom., cov: 31)
  • Exomes 𝑓: 0.56 (11 hom.)
• Consequence: GABRR2 ENST00000402938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.289-1130A>G		intron_variant		ENST00000402938.4	NP_002034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.289-1130A>G		intron_variant		1	NM_002043.5	ENSP00000386029	P1
GABRR2	ENST00000602808.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99472 AN: 151876 Hom.: 33043 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.565 AC: 35 AN: 62 Hom.: 11 Cov.: 0 AF XY: 0.550 AC XY: 22 AN XY: 40

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.655 AC: 99574 AN: 151994 Hom.: 33093 Cov.: 31 AF XY: 0.656 AC XY: 48747 AN XY: 74300

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.657

Alfa AF: 0.601 Hom.: 26565

Bravo AF: 0.657

Asia WGS AF: 0.722 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs282121; hg19: chr6-89980083;