rs3756980

chr6-52987181-A-G

Variant summary

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

The NM_001512.4(GSTA4):c.139+176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,132 control chromosomes in the GnomAD database, including 2,505 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 0.17 (2505 hom., cov: 32)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA4	NM_001512.4	c.139+176T>C		intron_variant		ENST00000370963.9
GSTA4	XM_005249035.5	c.139+176T>C		intron_variant
GSTA4	XM_011514534.4	c.29-1598T>C		intron_variant
GSTA4	XM_011514535.4	c.29-1598T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA4	ENST00000370963.9	c.139+176T>C		intron_variant		1	NM_001512.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26332 AN: 152014 Hom.: 2498 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.173 AC: 26352 AN: 152132 Hom.: 2505 Cov.: 32 AF XY: 0.176 AC XY: 13122 AN XY: 74358

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.178

Alfa AF: 0.193 Hom.: 3444

Bravo AF: 0.162

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.57

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: rs3756980; hg19: chr6-52851979; COSMIC: COSV63955574;