rs2274760

Positions:

• chr6-52985357-G-C

Variant summary

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

The NM_001512.4(GSTA4):​c.272+94C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,202,564 control chromosomes in the GnomAD database, including 8,526 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 0.088 (857 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7669 hom.)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

Genes affected

GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

GSTA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.272+94C>G		intron_variant		ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.272+94C>G		intron_variant			XP_005249092.1
GSTA4	XM_011514534.4	c.161+94C>G		intron_variant			XP_011512836.1
GSTA4	XM_011514535.4	c.161+94C>G		intron_variant			XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.272+94C>G		intron_variant		1	NM_001512.4	ENSP00000360002.4

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13465 AN: 152058 Hom.: 858 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0888

GnomAD4 exome AF: 0.115 AC: 120635 AN: 1050388 Hom.: 7669 AF XY: 0.114 AC XY: 60073 AN XY: 527210

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.0581

Gnomad4 ASJ exome AF: 0.0853

Gnomad4 EAS exome AF: 0.0605

Gnomad4 SAS exome AF: 0.0724

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0884 AC: 13458 AN: 152176 Hom.: 857 Cov.: 32 AF XY: 0.0921 AC XY: 6848 AN XY: 74386

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.0595

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.102 Hom.: 143

Bravo AF: 0.0748

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.62

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: rs2274760; hg19: chr6-52850155; COSMIC: COSV63955755;