15-27179760-A-T

Variant names:

• chr15-27179760-A-T
• rs208129
• NM_033223.5:c.271-147049A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.271-147049A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,978 control chromosomes in the GnomAD database, including 11,321 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 0.38 (11321 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.271-147049A>T		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.271-147049A>T		intron_variant	Intron 3 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.271-147049A>T		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.271-147049A>T		intron_variant	Intron 3 of 5	2		ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58005 AN: 151860 Hom.: 11303 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.382 AC: 58056 AN: 151978 Hom.: 11321 Cov.: 32 AF XY: 0.383 AC XY: 28482 AN XY: 74282

African (AFR) AF: 0.308 AC: 12776 AN: 41424

American (AMR) AF: 0.454 AC: 6924 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2249 AN: 5156

South Asian (SAS) AF: 0.458 AC: 2205 AN: 4814

European-Finnish (FIN) AF: 0.359 AC: 3789 AN: 10562

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27524 AN: 67970

Other (OTH) AF: 0.393 AC: 831 AN: 2112

Alfa AF: 0.391 Hom.: 1454

Bravo AF: 0.384

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.48
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs208129; hg19: chr15-27424907;