rs4986947

Positions:

• chr6-52984432-G-A
• chr6-52984432-G-T

Variant summary

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

The NM_001512.4(GSTA4):​c.414+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,583,256 control chromosomes in the GnomAD database, including 3,049 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: 0.059 (2821 hom.)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857

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=-0.91).
• 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.414+32C>T		intron_variant		ENST00000370963.9
GSTA4	XM_005249035.5	c.414+32C>T		intron_variant
GSTA4	XM_011514534.4	c.303+32C>T		intron_variant
GSTA4	XM_011514535.4	c.303+32C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA4	ENST00000370963.9	c.414+32C>T		intron_variant		1	NM_001512.4	P1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7062 AN: 152168 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0463

GnomAD3 exomes AF: 0.0482 AC: 11142 AN: 231044 Hom.: 330 AF XY: 0.0496 AC XY: 6217 AN XY: 125418

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.0276

Gnomad ASJ exome AF: 0.0732

Gnomad EAS exome AF: 0.000233

Gnomad SAS exome AF: 0.0325

Gnomad FIN exome AF: 0.0628

Gnomad NFE exome AF: 0.0654

Gnomad OTH exome AF: 0.0494

GnomAD4 exome AF: 0.0593 AC: 84897 AN: 1430970 Hom.: 2821 Cov.: 30 AF XY: 0.0588 AC XY: 41866 AN XY: 712072

Gnomad4 AFR exome AF: 0.00850

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.0344

Gnomad4 FIN exome AF: 0.0659

Gnomad4 NFE exome AF: 0.0656

Gnomad4 OTH exome AF: 0.0546

GnomAD4 genome AF: 0.0464 AC: 7059 AN: 152286 Hom.: 228 Cov.: 32 AF XY: 0.0447 AC XY: 3332 AN XY: 74478

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.0727

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0631 Hom.: 486

Bravo AF: 0.0443

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.20

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: rs4986947; hg19: chr6-52849230;