rs2061051

Positions:

• chr15-27275664-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.271-51145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,042 control chromosomes in the GnomAD database, including 31,291 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 (31291 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.271-51145G>A		intron_variant		ENST00000615808.5
GABRG3	NM_001270873.2	c.271-51145G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.271-51145G>A		intron_variant		1	NM_033223.5	P1
GABRG3	ENST00000554696.5	c.96+4027G>A		intron_variant		3
GABRG3	ENST00000555083.5	c.271-51145G>A		intron_variant		2
GABRG3	ENST00000554786.1	n.97+4027G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96309 AN: 151926 Hom.: 31258 Cov.: 33

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.634 AC: 96388 AN: 152042 Hom.: 31291 Cov.: 33 AF XY: 0.629 AC XY: 46729 AN XY: 74312

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.561

Alfa AF: 0.650 Hom.: 5273

Bravo AF: 0.631

Asia WGS AF: 0.366 AC: 1271 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	0.85
DANN	Benign	0.30

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: rs2061051; hg19: chr15-27520811;