rs12148908

chr15-27200602-T-Cchr15-27200602-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
GABRG3	NM_033223.5	c.271-126207T>C		intron_variant		ENST00000615808.5
GABRG3	NM_001270873.2	c.271-126207T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.271-126207T>C		intron_variant		1	NM_033223.5	P1
GABRG3	ENST00000555083.5	c.271-126207T>C		intron_variant		2

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.315

Alfa AF: 0.311 Hom.: 10846

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

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: rs12148908; hg19: chr15-27445749;