6-52985357-G-C

Variant names:

• chr6-52985357-G-C
• rs2274760
• NM_001512.4:c.272+94C>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.272+94C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,202,564 control chromosomes in the GnomAD database, including 8,526 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 0.088 (857 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7669 hom.)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	NM_001512.4	MANE Select	c.272+94C>G		intron	N/A	NP_001503.1	O15217-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	ENST00000370963.9	TSL:1 MANE Select	c.272+94C>G		intron	N/A	ENSP00000360002.4	O15217-1
	GSTA4	ENST00000370959.1	TSL:5	c.272+94C>G		intron	N/A	ENSP00000359998.1	O15217-1
	GSTA4	ENST00000887782.1		c.272+94C>G		intron	N/A	ENSP00000557841.1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13465 AN: 152058 Hom.: 858 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0888

GnomAD4 exome AF: 0.115 AC: 120635 AN: 1050388 Hom.: 7669 AF XY: 0.114 AC XY: 60073 AN XY: 527210

African (AFR) AF: 0.0176 AC: 435 AN: 24752

American (AMR) AF: 0.0581 AC: 1598 AN: 27498

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 1535 AN: 17992

East Asian (EAS) AF: 0.0605 AC: 2236 AN: 36954

South Asian (SAS) AF: 0.0724 AC: 4360 AN: 60222

European-Finnish (FIN) AF: 0.214 AC: 10431 AN: 48642

Middle Eastern (MID) AF: 0.0801 AC: 300 AN: 3744

European-Non Finnish (NFE) AF: 0.121 AC: 95070 AN: 785072

Other (OTH) AF: 0.103 AC: 4670 AN: 45512

GnomAD4 genome AF: 0.0884 AC: 13458 AN: 152176 Hom.: 857 Cov.: 32 AF XY: 0.0921 AC XY: 6848 AN XY: 74386

African (AFR) AF: 0.0208 AC: 865 AN: 41530

American (AMR) AF: 0.0626 AC: 958 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.0595 AC: 308 AN: 5176

South Asian (SAS) AF: 0.0669 AC: 322 AN: 4812

European-Finnish (FIN) AF: 0.228 AC: 2409 AN: 10564

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7877 AN: 68008

Other (OTH) AF: 0.0879 AC: 186 AN: 2116

Alfa AF: 0.102 Hom.: 143

Bravo AF: 0.0748

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		0.15
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: rs2274760; hg19: chr6-52850155; COSMIC: COSV63955755;