12-16352362-G-A

Variant names:

• chr12-16352362-G-A
• rs1913263
• NM_020300.5:c.-22-1869G>A

Variant summary

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

The ENST00000396210.8(MGST1):​c.-22-1869G>A 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 151,982 control chromosomes in the GnomAD database, including 37,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.70 (37658 hom., cov: 32)
• Consequence: MGST1 ENST00000396210.8 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.341
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396210.8. 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
	MGST1	NM_020300.5	MANE Select	c.-22-1869G>A		intron	N/A	NP_064696.1
	MGST1	NM_001414355.1		c.-22-1869G>A		intron	N/A	NP_001401284.1
	MGST1	NM_001414356.1		c.-22-1869G>A		intron	N/A	NP_001401285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	ENST00000396210.8	TSL:1 MANE Select	c.-22-1869G>A		intron	N/A	ENSP00000379513.3
	MGST1	ENST00000535309.5	TSL:1	c.-22-1869G>A		intron	N/A	ENSP00000438308.1
	MGST1	ENST00000542256.5	TSL:1	n.57+4652G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106444 AN: 151866 Hom.: 37603 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.701 AC: 106554 AN: 151982 Hom.: 37658 Cov.: 32 AF XY: 0.697 AC XY: 51734 AN XY: 74262

African (AFR) AF: 0.682 AC: 28263 AN: 41432

American (AMR) AF: 0.681 AC: 10402 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2712 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2444 AN: 5146

South Asian (SAS) AF: 0.583 AC: 2800 AN: 4806

European-Finnish (FIN) AF: 0.718 AC: 7598 AN: 10576

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

European-Non Finnish (NFE) AF: 0.735 AC: 49931 AN: 67966

Other (OTH) AF: 0.728 AC: 1539 AN: 2114

Alfa AF: 0.724 Hom.: 179393

Bravo AF: 0.697

Asia WGS AF: 0.524 AC: 1819 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.35
PhyloP100		-0.34
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: rs1913263; hg19: chr12-16505296;