rs1051775

Variant names:

• chr6-52794164-T-C
• rs1051775
• NM_145740.5:c.375A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145740.5(GSTA1):​c.375A>G​(p.Lys125Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,472 control chromosomes in the GnomAD database, including 129,166 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 0.30 (8859 hom., cov: 31)
  • Exomes 𝑓: 0.40 (120307 hom.)
• Consequence: GSTA1 NM_145740.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA1	NM_145740.5	c.375A>G	p.Lys125Lys	synonymous_variant	Exon 5 of 7	ENST00000334575.6	NP_665683.1
GSTA1	NM_001319059.2	c.96A>G	p.Lys32Lys	synonymous_variant	Exon 4 of 6		NP_001305988.1
GSTA1	XM_005249034.5	c.375A>G	p.Lys125Lys	synonymous_variant	Exon 5 of 6		XP_005249091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA1	ENST00000334575.6	c.375A>G	p.Lys125Lys	synonymous_variant	Exon 5 of 7	1	NM_145740.5	ENSP00000335620.5
GSTA1	ENST00000476213.1	n.429A>G		non_coding_transcript_exon_variant	Exon 4 of 4	5
GSTA1	ENST00000493331.5	n.272A>G		non_coding_transcript_exon_variant	Exon 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46317 AN: 151946 Hom.: 8862 Cov.: 31

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.321

GnomAD3 exomes AF: 0.342 AC: 86100 AN: 251442 Hom.: 16809 AF XY: 0.356 AC XY: 48428 AN XY: 135892

Gnomad AFR exome AF: 0.0889

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.438

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.397 AC: 580097 AN: 1461408 Hom.: 120307 Cov.: 42 AF XY: 0.398 AC XY: 289060 AN XY: 727004

Gnomad4 AFR exome AF: 0.0846

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.305 AC: 46318 AN: 152064 Hom.: 8859 Cov.: 31 AF XY: 0.304 AC XY: 22576 AN XY: 74320

Gnomad4 AFR AF: 0.0942

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.317

Alfa AF: 0.375 Hom.: 5054

Bravo AF: 0.282

Asia WGS AF: 0.238 AC: 826 AN: 3478

EpiCase AF: 0.423

EpiControl AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051775; hg19: chr6-52658962; COSMIC: COSV58014505;