rs12591360

Variant names:

• chr15-27409146-G-A
• rs12591360
• NM_033223.5:c.575-71504G>A

Variant summary

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

The NM_033223.5(GABRG3):​c.575-71504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 151,648 control chromosomes in the GnomAD database, including 964 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 0.11 (964 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 0 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 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.575-71504G>A		intron	N/A	NP_150092.2	Q99928-1
	GABRG3	NM_001270873.2		c.575-71504G>A		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.575-71504G>A		intron	N/A	ENSP00000479113.1	Q99928-1
	GABRG3	ENST00000333743.10	TSL:5	c.38-71504G>A		intron	N/A	ENSP00000331912.7	A0A0A0MR73
	GABRG3	ENST00000554696.5	TSL:3	c.401-71504G>A		intron	N/A	ENSP00000451862.1	H0YJP1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16554 AN: 151534 Hom.: 962 Cov.: 32

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.109 AC: 16569 AN: 151648 Hom.: 964 Cov.: 32 AF XY: 0.111 AC XY: 8222 AN XY: 74086

African (AFR) AF: 0.0975 AC: 4032 AN: 41360

American (AMR) AF: 0.0869 AC: 1326 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3464

East Asian (EAS) AF: 0.181 AC: 933 AN: 5142

South Asian (SAS) AF: 0.196 AC: 944 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1074 AN: 10388

Middle Eastern (MID) AF: 0.222 AC: 64 AN: 288

European-Non Finnish (NFE) AF: 0.110 AC: 7468 AN: 67916

Other (OTH) AF: 0.122 AC: 256 AN: 2106

Alfa AF: 0.106 Hom.: 132

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.12
PhyloP100		-0.83
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: rs12591360; hg19: chr15-27654292;