chr3-97993153-G-A

Variant names:

• chr3-97993153-G-A
• rs937130
• NM_001105580.3:c.908-105C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GABRR3	NM_001105580.3	c.908-105C>T		intron_variant	Intron 8 of 9	ENST00000472788.6	NP_001099050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR3	ENST00000472788.6	c.908-105C>T		intron_variant	Intron 8 of 9	5	NM_001105580.3	ENSP00000420790.1

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

African (AFR) AF: 0.214 AC: 3597 AN: 16842

American (AMR) AF: 0.405 AC: 6497 AN: 16048

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 7248 AN: 13922

East Asian (EAS) AF: 0.540 AC: 16088 AN: 29790

South Asian (SAS) AF: 0.304 AC: 10425 AN: 34278

European-Finnish (FIN) AF: 0.506 AC: 21332 AN: 42166

Middle Eastern (MID) AF: 0.438 AC: 1016 AN: 2322

European-Non Finnish (NFE) AF: 0.471 AC: 232273 AN: 492832

Other (OTH) AF: 0.446 AC: 14601 AN: 32740

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

African (AFR) AF: 0.231 AC: 9589 AN: 41478

American (AMR) AF: 0.434 AC: 6630 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2644 AN: 5156

South Asian (SAS) AF: 0.327 AC: 1571 AN: 4810

European-Finnish (FIN) AF: 0.499 AC: 5277 AN: 10568

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33469 AN: 67928

Other (OTH) AF: 0.439 AC: 923 AN: 2102

Alfa AF: 0.461 Hom.: 22516

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
PhyloP100		-0.78

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