15-26987381-T-G

Position:

• chr15-26987381-T-G

Variant summary

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

The NM_033223.5(GABRG3):​c.202+10231T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,120 control chromosomes in the GnomAD database, including 17,315 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 0.47 (17315 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.202+10231T>G		intron_variant		ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.202+10231T>G		intron_variant			NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.202+10231T>G		intron_variant		1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.202+10231T>G		intron_variant		2		ENSP00000452244.1
GABRG3	ENST00000553440.1	n.294+10231T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70866 AN: 152002 Hom.: 17306 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.466 AC: 70909 AN: 152120 Hom.: 17315 Cov.: 33 AF XY: 0.461 AC XY: 34290 AN XY: 74370

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.507

Alfa AF: 0.503 Hom.: 4026

Bravo AF: 0.457

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
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: rs2116526; hg19: chr15-27232528;