chr6-52978041-C-T

Position:

• chr6-52978041-C-T

Variant summary

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

The NM_001512.4(GSTA4):​c.*429G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 157,360 control chromosomes in the GnomAD database, including 2,743 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 (2716 hom., cov: 32)
  • Exomes 𝑓: 0.11 (27 hom.)
• Consequence: GSTA4 NM_001512.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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]

GSTA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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.*429G>A		3_prime_UTR_variant	7/7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.*429G>A		3_prime_UTR_variant	7/7		XP_005249092.1
GSTA4	XM_011514534.4	c.*429G>A		3_prime_UTR_variant	6/6		XP_011512836.1
GSTA4	XM_011514535.4	c.*429G>A		3_prime_UTR_variant	6/6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963	c.*429G>A		3_prime_UTR_variant	7/7	1	NM_001512.4	ENSP00000360002.4
GSTA4	ENST00000477599.5	n.1039G>A		non_coding_transcript_exon_variant	6/6	3
GSTA4	ENST00000486559.5	n.1605G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25900 AN: 151938 Hom.: 2696 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.109 AC: 579 AN: 5304 Hom.: 27 Cov.: 0 AF XY: 0.108 AC XY: 284 AN XY: 2626

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.0357

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.0812

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.171 AC: 25967 AN: 152056 Hom.: 2716 Cov.: 32 AF XY: 0.172 AC XY: 12755 AN XY: 74334

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.162

Alfa AF: 0.121 Hom.: 1618

Bravo AF: 0.184

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7496; hg19: chr6-52842839;