3-98019352-T-C

Variant summary

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

The NM_001105580.3(GABRR3):c.239-1630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,016 control chromosomes in the GnomAD database, including 6,220 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 0.26 (6220 hom., cov: 31)
• Consequence: GABRR3 NM_001105580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR3	NM_001105580.3	c.239-1630A>G		intron_variant		ENST00000472788.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR3	ENST00000472788.6	c.239-1630A>G		intron_variant		5	NM_001105580.3	P1
GABRR3	ENST00000470589.1	n.356-1630A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39715 AN: 151898 Hom.: 6223 Cov.: 31

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.261 AC: 39707 AN: 152016 Hom.: 6220 Cov.: 31 AF XY: 0.266 AC XY: 19745 AN XY: 74298

Gnomad4 AFR AF: 0.0767

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.272

Alfa AF: 0.308 Hom.: 3914

Bravo AF: 0.244

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.1
Dann	Benign	0.59

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: rs854579; hg19: chr3-97738196;