rs3759207

Positions:

• chr12-16363776-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414356.1(MGST1):​c.212-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,568,612 control chromosomes in the GnomAD database, including 72,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6386 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66328 hom.)
• Consequence: MGST1 NM_001414356.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

Genes affected

MGST1 (HGNC:7061): (microsomal glutathione S-transferase 1) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress. Several transcript variants, some non-protein coding and some protein coding, have been found for this gene. [provided by RefSeq, May 2012]

MGST1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	NM_020300.5	c.222-19T>C		intron_variant		ENST00000396210.8	NP_064696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000396210.8	c.222-19T>C		intron_variant		1	NM_020300.5	ENSP00000379513.3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43437 AN: 151898 Hom.: 6377 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.295

GnomAD3 exomes AF: 0.285 AC: 68103 AN: 239306 Hom.: 9932 AF XY: 0.288 AC XY: 37305 AN XY: 129634

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.303 AC: 429269 AN: 1416596 Hom.: 66328 Cov.: 29 AF XY: 0.303 AC XY: 212098 AN XY: 700384

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.286 AC: 43475 AN: 152016 Hom.: 6386 Cov.: 32 AF XY: 0.284 AC XY: 21134 AN XY: 74298

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.298

Alfa AF: 0.297 Hom.: 4917

Bravo AF: 0.283

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.44

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: rs3759207; hg19: chr12-16516710; COSMIC: COSV50566454;