chr6-52978333-G-T

Variant names:

• chr6-52978333-G-T
• rs367836
• NM_001512.4:c.*137C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001512.4(GSTA4):​c.*137C>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 0.601 in 800,630 control chromosomes in the GnomAD database, including 145,864 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 0.57 (24965 hom., cov: 31)
  • Exomes 𝑓: 0.61 (120899 hom.)
• Consequence: GSTA4 NM_001512.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• 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 rank	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.*137C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.*137C>A		3_prime_UTR_variant	Exon 7 of 7		XP_005249092.1
GSTA4	XM_011514534.4	c.*137C>A		3_prime_UTR_variant	Exon 6 of 6		XP_011512836.1
GSTA4	XM_011514535.4	c.*137C>A		3_prime_UTR_variant	Exon 6 of 6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.*137C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001512.4	ENSP00000360002.4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86637 AN: 151832 Hom.: 24960 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.609 AC: 394723 AN: 648678 Hom.: 120899 Cov.: 9 AF XY: 0.610 AC XY: 210271 AN XY: 344540

African (AFR) AF: 0.516 AC: 7289 AN: 14118

American (AMR) AF: 0.498 AC: 10758 AN: 21582

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 10891 AN: 18196

East Asian (EAS) AF: 0.775 AC: 24243 AN: 31298

South Asian (SAS) AF: 0.640 AC: 35133 AN: 54882

European-Finnish (FIN) AF: 0.539 AC: 24218 AN: 44908

Middle Eastern (MID) AF: 0.632 AC: 2557 AN: 4046

European-Non Finnish (NFE) AF: 0.609 AC: 260124 AN: 427028

Other (OTH) AF: 0.598 AC: 19510 AN: 32620

GnomAD4 genome AF: 0.570 AC: 86661 AN: 151952 Hom.: 24965 Cov.: 31 AF XY: 0.568 AC XY: 42184 AN XY: 74272

African (AFR) AF: 0.519 AC: 21496 AN: 41412

American (AMR) AF: 0.513 AC: 7842 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3827 AN: 5164

South Asian (SAS) AF: 0.648 AC: 3127 AN: 4822

European-Finnish (FIN) AF: 0.531 AC: 5591 AN: 10534

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40840 AN: 67962

Other (OTH) AF: 0.574 AC: 1204 AN: 2098

Alfa AF: 0.596 Hom.: 76154

Bravo AF: 0.567

Asia WGS AF: 0.658 AC: 2287 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	0.13
DANN	Benign	0.45
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs367836; hg19: chr6-52843131;