rs3957357

Variant names:

• chr6-52803889-A-G
• rs3957357
• NM_145740.5:c.-135T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_145740.5(GSTA1):​c.-135T>C variant causes a upstream gene 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: GSTA1 NM_145740.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

Genes affected

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

Verdict is Benign. Variant got -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
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

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.866

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.579

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

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.631

Alfa AF: 0.616 Hom.: 3546

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

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: rs3957357; hg19: chr6-52668687;