rs10772939

Positions:

• chr12-16456104-T-C

Variant summary

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

The XM_047428857.1(MGST1):​c.*16+72500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,624 control chromosomes in the GnomAD database, including 13,465 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 0.39 (13465 hom., cov: 32)
• Consequence: MGST1 XM_047428857.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	XM_047428857.1	c.*16+72500T>C		intron_variant			XP_047284813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000538857.1	n.482+72500T>C		intron_variant		3
MGST1	ENST00000539036.5	n.400+72500T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59081 AN: 151504 Hom.: 13463 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59102 AN: 151624 Hom.: 13465 Cov.: 32 AF XY: 0.388 AC XY: 28722 AN XY: 74064

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.418

Alfa AF: 0.494 Hom.: 33168

Bravo AF: 0.378

Asia WGS AF: 0.396 AC: 1369 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10772939; hg19: chr12-16609038;