rs937130

Positions:

• chr3-97993153-G-A

Variant summary

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

The NM_001105580.3(GABRR3):​c.908-105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 832,936 control chromosomes in the GnomAD database, including 88,801 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 0.41 (14032 hom., cov: 32)
  • Exomes 𝑓: 0.46 (74769 hom.)
• Consequence: GABRR3 NM_001105580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

Genes affected

GABRR3 (HGNC:17969): (gamma-aminobutyric acid type A receptor subunit rho3) The neurotransmitter gamma-aminobutyric acid (GABA) functions in the central nervous system to regulate synaptic transmission of neurons. This gene encodes one of three related subunits, which combine as homo- or hetero-pentamers to form GABA(C) receptors. In humans, some individuals contain a single-base polymorphism (dbSNP rs832032) that is predicted to inactivate the gene product. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR3	NM_001105580.3	c.908-105C>T		intron_variant		ENST00000472788.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR3	ENST00000472788.6	c.908-105C>T		intron_variant		5	NM_001105580.3	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62613 AN: 151878 Hom.: 14022 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.460 AC: 313077 AN: 680940 Hom.: 74769 AF XY: 0.457 AC XY: 155770 AN XY: 341092

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.412 AC: 62649 AN: 151996 Hom.: 14032 Cov.: 32 AF XY: 0.413 AC XY: 30691 AN XY: 74292

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.439

Alfa AF: 0.470 Hom.: 18012

Bravo AF: 0.400

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.51

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: rs937130; hg19: chr3-97711997; COSMIC: COSV72084437; COSMIC: COSV72084437;