chr6-52982104-T-C

Position:

• chr6-52982104-T-C

Variant summary

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

The NM_001512.4(GSTA4):​c.546+470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,154 control chromosomes in the GnomAD database, including 2,707 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 (2707 hom., cov: 32)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.546+470A>G		intron_variant		ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.546+470A>G		intron_variant			XP_005249092.1
GSTA4	XM_011514534.4	c.435+470A>G		intron_variant			XP_011512836.1
GSTA4	XM_011514535.4	c.435+470A>G		intron_variant			XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.546+470A>G		intron_variant		1	NM_001512.4	ENSP00000360002	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25888 AN: 152036 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.171 AC: 25955 AN: 152154 Hom.: 2707 Cov.: 32 AF XY: 0.171 AC XY: 12746 AN XY: 74384

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.161

Alfa AF: 0.124 Hom.: 1381

Bravo AF: 0.184

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.037
DANN	Benign	0.64

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: rs6904769; hg19: chr6-52846902;