6-52763237-C-T

Position:

• chr6-52763237-C-T

Variant summary

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

The NM_000846.5(GSTA2):​c.-31+207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,032 control chromosomes in the GnomAD database, including 43,943 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 0.75 (43943 hom., cov: 31)
• Consequence: GSTA2 NM_000846.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

Genes affected

GSTA2 (HGNC:4627): (glutathione S-transferase alpha 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of some drugs. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver. In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA2	NM_000846.5	c.-31+207G>A		intron_variant		ENST00000493422.3
GSTA2	XM_047418684.1	c.-165+207G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA2	ENST00000493422.3	c.-31+207G>A		intron_variant		1	NM_000846.5	P1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113673 AN: 151912 Hom.: 43883 Cov.: 31

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.749 AC: 113796 AN: 152032 Hom.: 43943 Cov.: 31 AF XY: 0.749 AC XY: 55624 AN XY: 74306

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.732

Alfa AF: 0.712 Hom.: 4816

Bravo AF: 0.771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2070774; hg19: chr6-52628035;