rs968671

chr15-27208761-A-G

Variant summary

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

The NM_033223.5(GABRG3):c.271-118048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,408 control chromosomes in the GnomAD database, including 168 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 0.034 (168 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.271-118048A>G		intron_variant		ENST00000615808.5
GABRG3	NM_001270873.2	c.271-118048A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.271-118048A>G		intron_variant		1	NM_033223.5	P1
GABRG3	ENST00000555083.5	c.271-118048A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5184 AN: 152116 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0115 AC: 2 AN: 174 Hom.: 0 AF XY: 0.0111 AC XY: 1 AN XY: 90

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0342 AC: 5203 AN: 152234 Hom.: 168 Cov.: 33 AF XY: 0.0329 AC XY: 2448 AN XY: 74424

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0426 Hom.: 33

Bravo AF: 0.0351

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.84
Dann	Benign	0.48

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: rs968671; hg19: chr15-27453908;