rs316141

Positions:

• chr6-52981360-A-G
• chr6-52981360-A-T

Variant summary

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

The NM_001512.4(GSTA4):​c.546+1214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,962 control chromosomes in the GnomAD database, including 24,464 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 0.56 (24464 hom., cov: 32)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA4	NM_001512.4	c.546+1214T>C		intron_variant		ENST00000370963.9
GSTA4	XM_005249035.5	c.546+1214T>C		intron_variant
GSTA4	XM_011514534.4	c.435+1214T>C		intron_variant
GSTA4	XM_011514535.4	c.435+1214T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA4	ENST00000370963.9	c.546+1214T>C		intron_variant		1	NM_001512.4	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85603 AN: 151844 Hom.: 24460 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.563 AC: 85624 AN: 151962 Hom.: 24464 Cov.: 32 AF XY: 0.561 AC XY: 41688 AN XY: 74270

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.569

Alfa AF: 0.600 Hom.: 35292

Bravo AF: 0.559

Asia WGS AF: 0.658 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.24

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: rs316141; hg19: chr6-52846158;