rs9672931

Variant names:

• chr15-27361255-G-A
• rs9672931
• NM_033223.5:c.574+32367G>A

Variant summary

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

The NM_033223.5(GABRG3):​c.574+32367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,984 control chromosomes in the GnomAD database, including 11,053 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 0.35 (11053 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

Genes affected

GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.574+32367G>A		intron_variant	Intron 5 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.574+32367G>A		intron_variant	Intron 5 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.574+32367G>A		intron_variant	Intron 5 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000333743.10	c.37+32367G>A		intron_variant	Intron 2 of 6	5		ENSP00000331912.7
GABRG3	ENST00000554696.5	c.400+32367G>A		intron_variant	Intron 3 of 5	3		ENSP00000451862.1
GABRG3	ENST00000555083.5	c.574+32367G>A		intron_variant	Intron 5 of 5	2		ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52664 AN: 151868 Hom.: 11030 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.347 AC: 52741 AN: 151984 Hom.: 11053 Cov.: 32 AF XY: 0.348 AC XY: 25853 AN XY: 74308

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.360

Alfa AF: 0.294 Hom.: 995

Bravo AF: 0.367

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.51

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: rs9672931; hg19: chr15-27606401;