rs8036270

Variant names:

• chr15-27218727-A-G
• rs8036270
• NM_033223.5:c.271-108082A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-27218727-A-G
• chr15-27218727-A-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.271-108082A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,046 control chromosomes in the GnomAD database, including 11,643 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 0.37 (11643 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.271-108082A>G		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.271-108082A>G		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.271-108082A>G		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.271-108082A>G		intron_variant	Intron 3 of 5	2		ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56580 AN: 151928 Hom.: 11630 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.372 AC: 56608 AN: 152046 Hom.: 11643 Cov.: 32 AF XY: 0.375 AC XY: 27893 AN XY: 74318

African (AFR) AF: 0.195 AC: 8104 AN: 41478

American (AMR) AF: 0.478 AC: 7293 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2335 AN: 5148

South Asian (SAS) AF: 0.577 AC: 2781 AN: 4820

European-Finnish (FIN) AF: 0.353 AC: 3730 AN: 10572

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29311 AN: 67980

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.422 Hom.: 23225

Bravo AF: 0.373

Asia WGS AF: 0.501 AC: 1739 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	2.0
DANN	Benign	0.37
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8036270; hg19: chr15-27463874;