rs1913262

Variant names:

• chr12-16352304-A-T
• rs1913262
• NM_020300.5:c.-22-1927A>T

Variant summary

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

The NM_020300.5(MGST1):​c.-22-1927A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,092 control chromosomes in the GnomAD database, including 37,693 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 0.70 (37693 hom., cov: 32)
• Consequence: MGST1 NM_020300.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST1	NM_020300.5	c.-22-1927A>T		intron_variant	Intron 1 of 3	ENST00000396210.8	NP_064696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000396210.8	c.-22-1927A>T		intron_variant	Intron 1 of 3	1	NM_020300.5	ENSP00000379513.3

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106523 AN: 151974 Hom.: 37637 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.701 AC: 106635 AN: 152092 Hom.: 37693 Cov.: 32 AF XY: 0.697 AC XY: 51802 AN XY: 74358

African (AFR) AF: 0.682 AC: 28298 AN: 41482

American (AMR) AF: 0.681 AC: 10412 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2716 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2446 AN: 5156

South Asian (SAS) AF: 0.583 AC: 2809 AN: 4816

European-Finnish (FIN) AF: 0.718 AC: 7608 AN: 10594

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49942 AN: 67978

Other (OTH) AF: 0.729 AC: 1539 AN: 2112

Alfa AF: 0.718 Hom.: 4886

Bravo AF: 0.697

Asia WGS AF: 0.524 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.54
PhyloP100		-1.0
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: rs1913262; hg19: chr12-16505238;