rs4132750

Variant names:

• chr15-27406586-A-G
• rs4132750
• NM_033223.5:c.575-74064A>G

Variant summary

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

The NM_033223.5(GABRG3):​c.575-74064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,118 control chromosomes in the GnomAD database, including 2,976 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 0.17 (2976 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.575-74064A>G		intron	N/A	NP_150092.2	Q99928-1
	GABRG3	NM_001270873.2		c.575-74064A>G		intron	N/A	NP_001257802.1	Q99928-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.575-74064A>G		intron	N/A	ENSP00000479113.1	Q99928-1
	GABRG3	ENST00000333743.10	TSL:5	c.38-74064A>G		intron	N/A	ENSP00000331912.7	A0A0A0MR73
	GABRG3	ENST00000554696.5	TSL:3	c.401-74064A>G		intron	N/A	ENSP00000451862.1	H0YJP1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26384 AN: 152000 Hom.: 2969 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.174 AC: 26420 AN: 152118 Hom.: 2976 Cov.: 32 AF XY: 0.173 AC XY: 12894 AN XY: 74376

African (AFR) AF: 0.324 AC: 13423 AN: 41472

American (AMR) AF: 0.108 AC: 1654 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3468

East Asian (EAS) AF: 0.181 AC: 933 AN: 5150

South Asian (SAS) AF: 0.197 AC: 950 AN: 4828

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10612

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.110 AC: 7492 AN: 67998

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.125 Hom.: 3604

Bravo AF: 0.178

Asia WGS AF: 0.217 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.57
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4132750;

hg19: chr15-27651732;