chr6-52763237-C-T

Variant names:

• chr6-52763237-C-T
• rs2070774
• NM_000846.5:c.-31+207G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GSTA2	NM_000846.5	c.-31+207G>A		intron_variant	Intron 1 of 6	ENST00000493422.3	NP_000837.3
GSTA2	XM_047418684.1	c.-165+207G>A		intron_variant	Intron 1 of 7		XP_047274640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA2	ENST00000493422.3	c.-31+207G>A		intron_variant	Intron 1 of 6	1	NM_000846.5	ENSP00000420168.1

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

African (AFR) AF: 0.939 AC: 39004 AN: 41528

American (AMR) AF: 0.783 AC: 11953 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3468

East Asian (EAS) AF: 0.873 AC: 4510 AN: 5168

South Asian (SAS) AF: 0.670 AC: 3218 AN: 4806

European-Finnish (FIN) AF: 0.620 AC: 6521 AN: 10524

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43973 AN: 67956

Other (OTH) AF: 0.732 AC: 1547 AN: 2114

Alfa AF: 0.719 Hom.: 5131

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
PhyloP100		-0.88
PromoterAI		0.0091	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070774; hg19: chr6-52628035;