rs1492053

Positions:

• chr3-98002199-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.755-432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,940 control chromosomes in the GnomAD database, including 9,527 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 0.34 (9527 hom., cov: 32)
• Consequence: GABRR3 NM_001105580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR3	NM_001105580.3	c.755-432C>T		intron_variant		ENST00000472788.6	NP_001099050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR3	ENST00000472788.6	c.755-432C>T		intron_variant		5	NM_001105580.3	ENSP00000420790	P1
GABRR3	ENST00000470589.1	n.502-432C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52105 AN: 151822 Hom.: 9518 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.343 AC: 52134 AN: 151940 Hom.: 9527 Cov.: 32 AF XY: 0.346 AC XY: 25696 AN XY: 74250

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.371

Alfa AF: 0.364 Hom.: 2055

Bravo AF: 0.338

Asia WGS AF: 0.415 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.53

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: rs1492053; hg19: chr3-97721043;