NM_001105580.3:c.908-1610G>A

Variant names:

• chr3-97994658-C-T
• rs7638369
• NM_001105580.3:c.908-1610G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105580.3(GABRR3):​c.908-1610G>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
• Publications: 4 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=-0.78).
• 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 rank	MANE	Protein	UniProt
GABRR3	NM_001105580.3	c.908-1610G>A		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.908-1610G>A		intron_variant	Intron 8 of 9	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

African (AFR) AF: 0.576 AC: 23894 AN: 41486

American (AMR) AF: 0.336 AC: 5138 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3468

East Asian (EAS) AF: 0.180 AC: 932 AN: 5168

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4812

European-Finnish (FIN) AF: 0.346 AC: 3653 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23442 AN: 67992

Other (OTH) AF: 0.361 AC: 761 AN: 2110

Alfa AF: 0.355 Hom.: 30181

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
PhyloP100		-1.8

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: rs7638369; hg19: chr3-97713502;