rs1802061

chr6-52984527-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001512.4(GSTA4):c.351G>A(p.Gln117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 1,612,926 control chromosomes in the GnomAD database, including 3,179 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 0.046 (228 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2951 hom.)
• Consequence: GSTA4 NM_001512.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-2.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA4	NM_001512.4	c.351G>A	p.Gln117=	synonymous_variant	5/7	ENST00000370963.9
GSTA4	XM_005249035.5	c.351G>A	p.Gln117=	synonymous_variant	5/7
GSTA4	XM_011514534.4	c.240G>A	p.Gln80=	synonymous_variant	4/6
GSTA4	XM_011514535.4	c.240G>A	p.Gln80=	synonymous_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA4	ENST00000370963.9	c.351G>A	p.Gln117=	synonymous_variant	5/7	1	NM_001512.4	P1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7061 AN: 152100 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0492 AC: 12356 AN: 251334 Hom.: 379 AF XY: 0.0503 AC XY: 6837 AN XY: 135838

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0291

Gnomad ASJ exome AF: 0.0788

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0350

Gnomad FIN exome AF: 0.0639

Gnomad NFE exome AF: 0.0670

Gnomad OTH exome AF: 0.0505

GnomAD4 exome AF: 0.0603 AC: 88079 AN: 1460708 Hom.: 2951 Cov.: 31 AF XY: 0.0597 AC XY: 43412 AN XY: 726728

Gnomad4 AFR exome AF: 0.00908

Gnomad4 AMR exome AF: 0.0299

Gnomad4 ASJ exome AF: 0.0758

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.0666

Gnomad4 NFE exome AF: 0.0669

Gnomad4 OTH exome AF: 0.0556

GnomAD4 genome AF: 0.0464 AC: 7058 AN: 152218 Hom.: 228 Cov.: 32 AF XY: 0.0448 AC XY: 3335 AN XY: 74420

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0470

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0626 Hom.: 616

Bravo AF: 0.0443

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.0679

EpiControl AF: 0.0684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.93
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1802061; hg19: chr6-52849325;