rs1570028

Positions:

• chr6-89302716-G-A
• chr6-89302716-G-T

Variant summary

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

The NM_002043.5(GABRR2):​c.114-2851C>T variant causes a intron change. The variant allele was found at a frequency of 0.533 in 1,355,220 control chromosomes in the GnomAD database, including 200,823 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 0.60 (29030 hom., cov: 32)
  • Exomes 𝑓: 0.52 (171793 hom.)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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]

TUBB3P1 (HGNC:42339): (tubulin beta 3 class III pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) 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.114-2851C>T		intron_variant		ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.189-2851C>T		intron_variant			XP_047274555.1
TUBB3P1		n.89302716G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.114-2851C>T		intron_variant		1	NM_002043.5	ENSP00000386029.4
TUBB3P1	ENST00000405796.1	n.934G>A		non_coding_transcript_exon_variant	1/1	6
GABRR2	ENST00000602808.1	n.248-2851C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91775 AN: 151958 Hom.: 28985 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.524 AC: 630559 AN: 1203142 Hom.: 171793 Cov.: 25 AF XY: 0.532 AC XY: 321423 AN XY: 603944

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.766

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.604 AC: 91879 AN: 152078 Hom.: 29030 Cov.: 32 AF XY: 0.612 AC XY: 45460 AN XY: 74322

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.593

Alfa AF: 0.549 Hom.: 2980

Bravo AF: 0.603

Asia WGS AF: 0.764 AC: 2659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.8
DANN	Benign	0.65

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: rs1570028; hg19: chr6-90012435; COSMIC: COSV68266120;