rs3097493

chr15-27525387-G-C

Variant summary

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

The NM_033223.5(GABRG3):c.866-2046G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,998 control chromosomes in the GnomAD database, including 30,893 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 0.63 (30893 hom., cov: 31)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807

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]

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.866-2046G>C		intron_variant		ENST00000615808.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.866-2046G>C		intron_variant		1	NM_033223.5	P1
	ENST00000556642.1	n.85+15726C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94946 AN: 151880 Hom.: 30848 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.625 AC: 95049 AN: 151998 Hom.: 30893 Cov.: 31 AF XY: 0.623 AC XY: 46252 AN XY: 74274

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.623

Alfa AF: 0.581 Hom.: 3320

Bravo AF: 0.648

Asia WGS AF: 0.578 AC: 2010 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	0.75
Dann	Benign	0.43

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: rs3097493; hg19: chr15-27770533;