rs405729

Positions:

• chr6-52977983-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.*487A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,888 control chromosomes in the GnomAD database, including 20,522 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 0.51 (20434 hom., cov: 33)
  • Exomes 𝑓: 0.46 (88 hom.)
• Consequence: GSTA4 NM_001512.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

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 (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.*487A>G		3_prime_UTR_variant	7/7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.*487A>G		3_prime_UTR_variant	7/7		XP_005249092.1
GSTA4	XM_011514534.4	c.*487A>G		3_prime_UTR_variant	6/6		XP_011512836.1
GSTA4	XM_011514535.4	c.*487A>G		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.*487A>G		3_prime_UTR_variant	7/7	1	NM_001512.4	ENSP00000360002.4
GSTA4	ENST00000477599.5	n.1097A>G		non_coding_transcript_exon_variant	6/6	3
GSTA4	ENST00000486559.5	n.1663A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78108 AN: 151998 Hom.: 20430 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.460 AC: 355 AN: 772 Hom.: 88 Cov.: 0 AF XY: 0.488 AC XY: 207 AN XY: 424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.929

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.514 AC: 78133 AN: 152116 Hom.: 20434 Cov.: 33 AF XY: 0.513 AC XY: 38166 AN XY: 74358

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.521

Alfa AF: 0.539 Hom.: 45427

Bravo AF: 0.511

Asia WGS AF: 0.643 AC: 2237 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	4.3
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs405729; hg19: chr6-52842781;