rs12148267

Positions:

• chr15-27052103-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.270+25282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,228 control chromosomes in the GnomAD database, including 1,922 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 0.14 (1922 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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]

GABRG3-AS1 (HGNC:40249): (GABRG3 antisense RNA 1)

LOC124903449 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.270+25282G>A		intron_variant		ENST00000615808.5
LOC124903449	XR_007064545.1	n.221-11429C>T		intron_variant, non_coding_transcript_variant
GABRG3	NM_001270873.2	c.270+25282G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+25282G>A		intron_variant		1	NM_033223.5	P1
GABRG3-AS1	ENST00000660679.1	n.377-11429C>T		intron_variant, non_coding_transcript_variant
GABRG3	ENST00000555083.5	c.270+25282G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21252 AN: 152110 Hom.: 1923 Cov.: 33

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.140 AC: 21248 AN: 152228 Hom.: 1922 Cov.: 33 AF XY: 0.139 AC XY: 10309 AN XY: 74424

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.166

Alfa AF: 0.186 Hom.: 2977

Bravo AF: 0.134

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.63

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: rs12148267; hg19: chr15-27297250;