rs12148908

Variant names:

• chr15-27200602-T-C
• rs12148908
• NM_033223.5:c.271-126207T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-27200602-T-C
• chr15-27200602-T-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.271-126207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,022 control chromosomes in the GnomAD database, including 6,034 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 0.26 (6034 hom., cov: 31)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.271-126207T>C		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.271-126207T>C		intron_variant	Intron 3 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.271-126207T>C		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.271-126207T>C		intron_variant	Intron 3 of 5	2		ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40243 AN: 151904 Hom.: 6019 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.265 AC: 40268 AN: 152022 Hom.: 6034 Cov.: 31 AF XY: 0.271 AC XY: 20120 AN XY: 74286

African (AFR) AF: 0.119 AC: 4923 AN: 41462

American (AMR) AF: 0.373 AC: 5690 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5158

South Asian (SAS) AF: 0.461 AC: 2215 AN: 4808

European-Finnish (FIN) AF: 0.276 AC: 2923 AN: 10572

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20781 AN: 67974

Other (OTH) AF: 0.315 AC: 664 AN: 2106

Alfa AF: 0.305 Hom.: 14282

Bravo AF: 0.263

Asia WGS AF: 0.371 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.76
PhyloP100		-0.24
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: rs12148908; hg19: chr15-27445749;