rs4986947

Variant names:

• chr6-52984432-G-A
• rs4986947
• NM_001512.4:c.414+32C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52984432-G-A
• chr6-52984432-G-T

Variant summary

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

The ENST00000370963.9(GSTA4):​c.414+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,583,256 control chromosomes in the GnomAD database, including 3,049 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 0.046 (228 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2821 hom.)
• Consequence: GSTA4 ENST00000370963.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370963.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	NM_001512.4	MANE Select	c.414+32C>T		intron	N/A	NP_001503.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	ENST00000370963.9	TSL:1 MANE Select	c.414+32C>T		intron	N/A	ENSP00000360002.4
	GSTA4	ENST00000370959.1	TSL:5	c.414+32C>T		intron	N/A	ENSP00000359998.1
	GSTA4	ENST00000370960.5	TSL:3	c.135+32C>T		intron	N/A	ENSP00000359999.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7062 AN: 152168 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0463

GnomAD2 exomes AF: 0.0482 AC: 11142 AN: 231044 AF XY: 0.0496

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.0276

Gnomad ASJ exome AF: 0.0732

Gnomad EAS exome AF: 0.000233

Gnomad FIN exome AF: 0.0628

Gnomad NFE exome AF: 0.0654

Gnomad OTH exome AF: 0.0494

GnomAD4 exome AF: 0.0593 AC: 84897 AN: 1430970 Hom.: 2821 Cov.: 30 AF XY: 0.0588 AC XY: 41866 AN XY: 712072

African (AFR) AF: 0.00850 AC: 272 AN: 32000

American (AMR) AF: 0.0290 AC: 1079 AN: 37258

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1837 AN: 25098

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39280

South Asian (SAS) AF: 0.0344 AC: 2817 AN: 81808

European-Finnish (FIN) AF: 0.0659 AC: 3491 AN: 53006

Middle Eastern (MID) AF: 0.0353 AC: 201 AN: 5686

European-Non Finnish (NFE) AF: 0.0656 AC: 71962 AN: 1097624

Other (OTH) AF: 0.0546 AC: 3233 AN: 59210

GnomAD4 genome AF: 0.0464 AC: 7059 AN: 152286 Hom.: 228 Cov.: 32 AF XY: 0.0447 AC XY: 3332 AN XY: 74478

African (AFR) AF: 0.0117 AC: 487 AN: 41566

American (AMR) AF: 0.0468 AC: 716 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4822

European-Finnish (FIN) AF: 0.0665 AC: 706 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4582 AN: 68014

Other (OTH) AF: 0.0458 AC: 97 AN: 2116

Alfa AF: 0.0615 Hom.: 572

Bravo AF: 0.0443

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.20
PhyloP100		0.86
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: rs4986947; hg19: chr6-52849230;