chr12-16352362-G-A

Position:

• chr12-16352362-G-A

Variant summary

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

The NM_020300.5(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 NM_020300.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.341

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

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 = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	NM_020300.5	c.-22-1869G>A		intron_variant		ENST00000396210.8	NP_064696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000396210.8	c.-22-1869G>A		intron_variant		1	NM_020300.5	ENSP00000379513	P1

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

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.728

Alfa AF: 0.731 Hom.: 83849

Bravo AF: 0.697

Asia WGS AF: 0.524 AC: 1819 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.35

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: rs1913263; hg19: chr12-16505296;