rs891802

chr15-27031472-C-T

Variant summary

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

The NM_033223.5(GABRG3):c.270+4651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,002 control chromosomes in the GnomAD database, including 31,870 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 0.65 (31870 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.270+4651C>T		intron_variant		ENST00000615808.5
GABRG3	NM_001270873.2	c.270+4651C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+4651C>T		intron_variant		1	NM_033223.5	P1
GABRG3	ENST00000555083.5	c.270+4651C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98227 AN: 151884 Hom.: 31844 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.647 AC: 98314 AN: 152002 Hom.: 31870 Cov.: 32 AF XY: 0.649 AC XY: 48217 AN XY: 74306

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.643

Alfa AF: 0.636 Hom.: 7250

Bravo AF: 0.648

Asia WGS AF: 0.671 AC: 2333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.11
Dann	Benign	0.61

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: rs891802; hg19: chr15-27276619;