chr3-97994658-C-T

Position:

• chr3-97994658-C-T

Variant summary

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

The NM_001105580.3(GABRR3):​c.908-1610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,092 control chromosomes in the GnomAD database, including 12,849 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 0.40 (12849 hom., cov: 33)
• Consequence: GABRR3 NM_001105580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR3	NM_001105580.3	c.908-1610G>A		intron_variant		ENST00000472788.6	NP_001099050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR3	ENST00000472788.6	c.908-1610G>A		intron_variant		5	NM_001105580.3	ENSP00000420790.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60131 AN: 151974 Hom.: 12821 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.396 AC: 60203 AN: 152092 Hom.: 12849 Cov.: 33 AF XY: 0.392 AC XY: 29118 AN XY: 74350

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.361

Alfa AF: 0.335 Hom.: 11591

Bravo AF: 0.401

Asia WGS AF: 0.271 AC: 944 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.58

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: rs7638369; hg19: chr3-97713502;