12-16360227-G-C

Position:

• chr12-16360227-G-C

Variant summary

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

The NM_020300.5(MGST1):​c.221+2528G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 475,272 control chromosomes in the GnomAD database, including 103,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (28002 hom., cov: 31)
  • Exomes 𝑓: 0.68 (75877 hom.)
• Consequence: MGST1 NM_020300.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.596

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 = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGST1	NM_020300.5	c.221+2528G>C		intron_variant		ENST00000396210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGST1	ENST00000396210.8	c.221+2528G>C		intron_variant		1	NM_020300.5	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89906 AN: 151846 Hom.: 27981 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.682 AC: 220492 AN: 323306 Hom.: 75877 AF XY: 0.683 AC XY: 105200 AN XY: 154052

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.694

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.693

Gnomad4 OTH exome AF: 0.649

GnomAD4 genome AF: 0.592 AC: 89967 AN: 151966 Hom.: 28002 Cov.: 31 AF XY: 0.588 AC XY: 43630 AN XY: 74258

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.602

Alfa AF: 0.648 Hom.: 16625

Bravo AF: 0.575

Asia WGS AF: 0.351 AC: 1222 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	1.0
DANN	Benign	0.59

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: rs4149197; hg19: chr12-16513161;