6-52978631-A-G

Variant names:

• chr6-52978631-A-G
• rs3734431
• NM_001512.4:c.547-39T>C

Variant summary

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

The NM_001512.4(GSTA4):​c.547-39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,538,188 control chromosomes in the GnomAD database, including 4,625 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 0.077 (458 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4167 hom.)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.547-39T>C		intron_variant	Intron 6 of 6	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.547-39T>C		intron_variant	Intron 6 of 6		XP_005249092.1
GSTA4	XM_011514534.4	c.436-39T>C		intron_variant	Intron 5 of 5		XP_011512836.1
GSTA4	XM_011514535.4	c.436-39T>C		intron_variant	Intron 5 of 5		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9	c.547-39T>C		intron_variant	Intron 6 of 6	1	NM_001512.4	ENSP00000360002.4

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11650 AN: 152124 Hom.: 457 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.0643

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.0844

GnomAD2 exomes AF: 0.0778 AC: 17738 AN: 227940 AF XY: 0.0790

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.0715

Gnomad ASJ exome AF: 0.0995

Gnomad EAS exome AF: 0.0773

Gnomad FIN exome AF: 0.0539

Gnomad NFE exome AF: 0.0821

Gnomad OTH exome AF: 0.0877

GnomAD4 exome AF: 0.0761 AC: 105486 AN: 1385946 Hom.: 4167 Cov.: 22 AF XY: 0.0766 AC XY: 53016 AN XY: 692150

African (AFR) AF: 0.0654 AC: 2010 AN: 30726

American (AMR) AF: 0.0710 AC: 2722 AN: 38312

Ashkenazi Jewish (ASJ) AF: 0.0941 AC: 2358 AN: 25068

East Asian (EAS) AF: 0.0680 AC: 2646 AN: 38940

South Asian (SAS) AF: 0.0841 AC: 6756 AN: 80368

European-Finnish (FIN) AF: 0.0540 AC: 2814 AN: 52128

Middle Eastern (MID) AF: 0.117 AC: 655 AN: 5588

European-Non Finnish (NFE) AF: 0.0766 AC: 80944 AN: 1057184

Other (OTH) AF: 0.0795 AC: 4581 AN: 57632

GnomAD4 genome AF: 0.0766 AC: 11660 AN: 152242 Hom.: 458 Cov.: 32 AF XY: 0.0764 AC XY: 5691 AN XY: 74446

African (AFR) AF: 0.0674 AC: 2801 AN: 41530

American (AMR) AF: 0.0884 AC: 1352 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 319 AN: 3468

East Asian (EAS) AF: 0.0644 AC: 334 AN: 5186

South Asian (SAS) AF: 0.0814 AC: 393 AN: 4826

European-Finnish (FIN) AF: 0.0484 AC: 513 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0840 AC: 5710 AN: 68016

Other (OTH) AF: 0.0830 AC: 175 AN: 2108

Alfa AF: 0.0839 Hom.: 1025

Bravo AF: 0.0785

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.33
DANN	Benign	0.60
PhyloP100		-0.0040
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: rs3734431; hg19: chr6-52843429;