6-52792754-C-T

Variant names:

• chr6-52792754-C-T
• rs4715326
• NM_145740.5:c.546+102G>A

Variant summary

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

The NM_145740.5(GSTA1):​c.546+102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,609,306 control chromosomes in the GnomAD database, including 293,306 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 0.64 (31321 hom., cov: 31)
  • Exomes 𝑓: 0.60 (261985 hom.)
• Consequence: GSTA1 NM_145740.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 21 publications found

Genes affected

GSTA1 (HGNC:4626): (glutathione S-transferase alpha 1) This gene encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. This action is an important step in detoxification of these compounds. This subfamily of enzymes has a particular role in protecting cells from reactive oxygen species and the products of peroxidation. Polymorphisms in this gene influence the ability of individuals to metabolize different drugs. This gene is located in a cluster of similar genes and pseudogenes on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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 = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145740.5. 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
	GSTA1	NM_145740.5	MANE Select	c.546+102G>A		intron	N/A	NP_665683.1
	GSTA1	NM_001319059.2		c.267+102G>A		intron	N/A	NP_001305988.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA1	ENST00000334575.6	TSL:1 MANE Select	c.546+102G>A		intron	N/A	ENSP00000335620.5
	GSTA1	ENST00000493331.5	TSL:2	n.443+102G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96508 AN: 151864 Hom.: 31300 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.630

GnomAD2 exomes AF: 0.641 AC: 159566 AN: 249056 AF XY: 0.631

Gnomad AFR exome AF: 0.697

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.547

Gnomad EAS exome AF: 0.877

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.596 AC: 868149 AN: 1457324 Hom.: 261985 Cov.: 42 AF XY: 0.596 AC XY: 432038 AN XY: 724968

African (AFR) AF: 0.700 AC: 23361 AN: 33364

American (AMR) AF: 0.762 AC: 33987 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 14151 AN: 26032

East Asian (EAS) AF: 0.874 AC: 34555 AN: 39518

South Asian (SAS) AF: 0.649 AC: 55627 AN: 85722

European-Finnish (FIN) AF: 0.563 AC: 29841 AN: 53020

Middle Eastern (MID) AF: 0.594 AC: 3402 AN: 5730

European-Non Finnish (NFE) AF: 0.574 AC: 636393 AN: 1109226

Other (OTH) AF: 0.613 AC: 36832 AN: 60112

GnomAD4 genome AF: 0.635 AC: 96577 AN: 151982 Hom.: 31321 Cov.: 31 AF XY: 0.639 AC XY: 47449 AN XY: 74292

African (AFR) AF: 0.701 AC: 29055 AN: 41444

American (AMR) AF: 0.702 AC: 10723 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1973 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4522 AN: 5178

South Asian (SAS) AF: 0.660 AC: 3169 AN: 4804

European-Finnish (FIN) AF: 0.564 AC: 5945 AN: 10544

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39075 AN: 67942

Other (OTH) AF: 0.633 AC: 1339 AN: 2114

Alfa AF: 0.582 Hom.: 40426

Bravo AF: 0.649

Asia WGS AF: 0.742 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.55
PhyloP100		0.27
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: rs4715326; hg19: chr6-52657552; COSMIC: COSV58015901; COSMIC: COSV58015901;