6-52982753-G-C

Variant names:

• chr6-52982753-G-C
• rs316133
• NM_001512.4:c.415-48C>G

Variant summary

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

The NM_001512.4(GSTA4):​c.415-48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,464,118 control chromosomes in the GnomAD database, including 261,834 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 (24509 hom., cov: 31)
  • Exomes 𝑓: 0.60 (237325 hom.)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623
• Publications: 13 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 (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001512.4. 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.415-48C>G		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.415-48C>G		intron	N/A	ENSP00000360002.4
	GSTA4	ENST00000370959.1	TSL:5	c.415-48C>G		intron	N/A	ENSP00000359998.1
	GSTA4	ENST00000370960.5	TSL:3	c.136-48C>G		intron	N/A	ENSP00000359999.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85677 AN: 151842 Hom.: 24504 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.566

GnomAD2 exomes AF: 0.589 AC: 144318 AN: 244902 AF XY: 0.597

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.603

Gnomad EAS exome AF: 0.738

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.600 AC: 786784 AN: 1312158 Hom.: 237325 Cov.: 18 AF XY: 0.602 AC XY: 397852 AN XY: 660652

African (AFR) AF: 0.490 AC: 14822 AN: 30270

American (AMR) AF: 0.489 AC: 20987 AN: 42938

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 15109 AN: 25194

East Asian (EAS) AF: 0.766 AC: 29829 AN: 38918

South Asian (SAS) AF: 0.642 AC: 52664 AN: 82080

European-Finnish (FIN) AF: 0.540 AC: 28352 AN: 52526

Middle Eastern (MID) AF: 0.633 AC: 3461 AN: 5470

European-Non Finnish (NFE) AF: 0.601 AC: 588584 AN: 979374

Other (OTH) AF: 0.595 AC: 32976 AN: 55388

GnomAD4 genome AF: 0.564 AC: 85699 AN: 151960 Hom.: 24509 Cov.: 31 AF XY: 0.562 AC XY: 41733 AN XY: 74274

African (AFR) AF: 0.497 AC: 20556 AN: 41398

American (AMR) AF: 0.509 AC: 7775 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3836 AN: 5172

South Asian (SAS) AF: 0.651 AC: 3138 AN: 4818

European-Finnish (FIN) AF: 0.531 AC: 5602 AN: 10554

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

European-Non Finnish (NFE) AF: 0.601 AC: 40851 AN: 67942

Other (OTH) AF: 0.569 AC: 1204 AN: 2116

Alfa AF: 0.581 Hom.: 4763

Bravo AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.28
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs316133; hg19: chr6-52847551; COSMIC: COSV63955847;