6-52983168-C-T

Variant names:

• chr6-52983168-C-T
• rs316132
• NM_001512.4:c.415-463G>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.415-463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,936 control chromosomes in the GnomAD database, including 24,496 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 (24496 hom., cov: 32)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 3 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=-0.88).
• 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 rank	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.415-463G>A		intron_variant	Intron 5 of 6	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.415-463G>A		intron_variant	Intron 5 of 6		XP_005249092.1
GSTA4	XM_011514534.4	c.304-463G>A		intron_variant	Intron 4 of 5		XP_011512836.1
GSTA4	XM_011514535.4	c.304-463G>A		intron_variant	Intron 4 of 5		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.415-463G>A		intron_variant	Intron 5 of 6	1	NM_001512.4	ENSP00000360002.4

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85664 AN: 151818 Hom.: 24492 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.646

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: 0.564 AC: 85685 AN: 151936 Hom.: 24496 Cov.: 32 AF XY: 0.562 AC XY: 41704 AN XY: 74242

African (AFR) AF: 0.497 AC: 20568 AN: 41412

American (AMR) AF: 0.509 AC: 7774 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3829 AN: 5166

South Asian (SAS) AF: 0.652 AC: 3136 AN: 4812

European-Finnish (FIN) AF: 0.530 AC: 5588 AN: 10538

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

European-Non Finnish (NFE) AF: 0.601 AC: 40854 AN: 67954

Other (OTH) AF: 0.569 AC: 1197 AN: 2104

Alfa AF: 0.594 Hom.: 44475

Bravo AF: 0.559

Asia WGS AF: 0.659 AC: 2291 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	4.1
DANN	Benign	0.53
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs316132; hg19: chr6-52847966;