rs2376481

Variant names:

• chr15-26975566-G-A
• rs2376481
• NM_033223.5:c.54-1436G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-26975566-G-A
• chr15-26975566-G-C
• chr15-26975566-G-T

Variant summary

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

The NM_033223.5(GABRG3):​c.54-1436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,006 control chromosomes in the GnomAD database, including 22,046 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 0.52 (22046 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.54-1436G>A		intron_variant	Intron 1 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.54-1436G>A		intron_variant	Intron 1 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.54-1436G>A		intron_variant	Intron 1 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.54-1436G>A		intron_variant	Intron 1 of 5	2		ENSP00000452244.1
GABRG3	ENST00000553440.1	n.146-1436G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79698 AN: 151888 Hom.: 22017 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.525 AC: 79779 AN: 152006 Hom.: 22046 Cov.: 33 AF XY: 0.521 AC XY: 38672 AN XY: 74294

African (AFR) AF: 0.712 AC: 29520 AN: 41480

American (AMR) AF: 0.440 AC: 6721 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2286 AN: 5168

South Asian (SAS) AF: 0.379 AC: 1821 AN: 4810

European-Finnish (FIN) AF: 0.532 AC: 5604 AN: 10528

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31016 AN: 67972

Other (OTH) AF: 0.499 AC: 1051 AN: 2106

Alfa AF: 0.471 Hom.: 46487

Bravo AF: 0.531

Asia WGS AF: 0.438 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.35
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2376481; hg19: chr15-27220713;