6-52801475-T-C

Position:

• chr6-52801475-T-C

Variant summary

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

The ENST00000334575.6(GSTA1):​c.-30-2178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,112 control chromosomes in the GnomAD database, including 31,324 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 0.64 (31324 hom., cov: 33)
• Consequence: GSTA1 ENST00000334575.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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=-0.88).
• 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/exons	MANE	Protein	UniProt
GSTA1	NM_145740.5	c.-30-2178A>G		intron_variant		ENST00000334575.6	NP_665683.1
GSTA1	NM_001319059.2	c.-176-2178A>G		intron_variant			NP_001305988.1
GSTA1	XM_005249034.5	c.-30-2178A>G		intron_variant			XP_005249091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA1	ENST00000334575.6	c.-30-2178A>G		intron_variant		1	NM_145740.5	ENSP00000335620	P1
GSTA1	ENST00000476213.1	n.77-2178A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96561 AN: 151994 Hom.: 31303 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.570

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: 0.629

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

GnomAD4 genome AF: 0.635 AC: 96630 AN: 152112 Hom.: 31324 Cov.: 33 AF XY: 0.638 AC XY: 47466 AN XY: 74354

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.632

Alfa AF: 0.597 Hom.: 13113

Bravo AF: 0.649

Asia WGS AF: 0.741 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.51

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: rs6917325; hg19: chr6-52666273;