rs3957357

Variant names:

• chr6-52803889-A-G
• rs3957357
• ENST00000778528.1:n.118+2686A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-52803889-A-G
• chr6-52803889-A-T

Variant summary

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

The ENST00000778528.1(ENSG00000301369):​n.118+2686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 211,512 control chromosomes in the GnomAD database, including 41,992 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 (30760 hom., cov: 32)
  • Exomes 𝑓: 0.60 (11232 hom.)
• Consequence: ENSG00000301369 ENST00000778528.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 96 publications found

Genes affected

ENSG00000301369 (HGNC:):

GSTA1 (HGNC:4626): (glutathione S-transferase alpha 1) This gene encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. This action is an important step in detoxification of these compounds. This subfamily of enzymes has a particular role in protecting cells from reactive oxygen species and the products of peroxidation. Polymorphisms in this gene influence the ability of individuals to metabolize different drugs. This gene is located in a cluster of similar genes and pseudogenes on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA1	NM_145740.5	c.-135T>C		upstream_gene_variant		ENST00000334575.6	NP_665683.1
GSTA1	NM_001319059.2	c.-281T>C		upstream_gene_variant			NP_001305988.1
GSTA1	XM_005249034.5	c.-135T>C		upstream_gene_variant			XP_005249091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301369	ENST00000778528.1	n.118+2686A>G		intron_variant	Intron 1 of 2
ENSG00000301369	ENST00000778529.1	n.63+2004A>G		intron_variant	Intron 1 of 2
GSTA1	ENST00000334575.6	c.-135T>C		upstream_gene_variant		1	NM_145740.5	ENSP00000335620.5
GSTA1	ENST00000476213.1	n.-29T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95666 AN: 151806 Hom.: 30741 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.603 AC: 35950 AN: 59590 Hom.: 11232 Cov.: 0 AF XY: 0.599 AC XY: 16551 AN XY: 27618

African (AFR) AF: 0.651 AC: 1721 AN: 2642

American (AMR) AF: 0.688 AC: 1189 AN: 1728

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 2038 AN: 3874

East Asian (EAS) AF: 0.866 AC: 7661 AN: 8848

South Asian (SAS) AF: 0.661 AC: 328 AN: 496

European-Finnish (FIN) AF: 0.522 AC: 24 AN: 46

Middle Eastern (MID) AF: 0.516 AC: 194 AN: 376

European-Non Finnish (NFE) AF: 0.544 AC: 19885 AN: 36552

Other (OTH) AF: 0.579 AC: 2910 AN: 5028

GnomAD4 genome AF: 0.630 AC: 95732 AN: 151922 Hom.: 30760 Cov.: 32 AF XY: 0.633 AC XY: 47024 AN XY: 74252

African (AFR) AF: 0.684 AC: 28345 AN: 41420

American (AMR) AF: 0.698 AC: 10665 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1963 AN: 3460

East Asian (EAS) AF: 0.873 AC: 4516 AN: 5172

South Asian (SAS) AF: 0.660 AC: 3179 AN: 4818

European-Finnish (FIN) AF: 0.563 AC: 5945 AN: 10564

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39010 AN: 67900

Other (OTH) AF: 0.631 AC: 1329 AN: 2106

Alfa AF: 0.606 Hom.: 45207

Bravo AF: 0.643

Asia WGS AF: 0.737 AC: 2560 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.43
PhyloP100		-2.2
PromoterAI		-0.098	Neutral
Mutation Taster		=299/1	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: rs3957357; hg19: chr6-52668687;