6-52803889-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000778528.1(ENSG00000301369):​n.118+2686A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000778528.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA1	NM_145740.5	MANE Select	c.-135T>A		upstream_gene	N/A	NP_665683.1	P08263
	GSTA1	NM_001319059.2		c.-281T>A		upstream_gene	N/A	NP_001305988.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000301369	ENST00000778528.1		n.118+2686A>T		intron	N/A
	ENSG00000301369	ENST00000778529.1		n.63+2004A>T		intron	N/A
	GSTA1	ENST00000334575.6	TSL:1 MANE Select	c.-135T>A		upstream_gene	N/A	ENSP00000335620.5	P08263

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 60004 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27806

African (AFR) AF: 0.00 AC: 0 AN: 2654

American (AMR) AF: 0.00 AC: 0 AN: 1738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3894

East Asian (EAS) AF: 0.00 AC: 0 AN: 8870

South Asian (SAS) AF: 0.00 AC: 0 AN: 498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36864

Other (OTH) AF: 0.00 AC: 0 AN: 5064

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.37
PhyloP100		-2.2
PromoterAI		-0.037	Neutral

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;