chr12-16366334-G-T

Position:

• chr12-16366334-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000535309.5(MGST1):​c.221+8635G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 152,120 control chromosomes in the GnomAD database, including 1,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency: Genomes: 𝑓 0.094 (1283 hom., cov: 32)
• Consequence: MGST1 ENST00000535309.5 intron
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 0.185

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-16366334-G-T is Benign according to our data. Variant chr12-16366334-G-T is described in ClinVar as [protective]. Clinvar id is 1693603.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGST1	NM_001267598.2	c.221+8635G>T		intron_variant
MGST1	NM_001414360.1	c.222-991G>T		intron_variant
MGST1	NM_001414362.1	c.222-991G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGST1	ENST00000535309.5	c.221+8635G>T		intron_variant		1
MGST1	ENST00000542256.5	n.153-991G>T		intron_variant, non_coding_transcript_variant		1
MGST1	ENST00000538857.1	n.244-991G>T		intron_variant, non_coding_transcript_variant		3
MGST1	ENST00000539036.5	n.302+8635G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14255 AN: 152002 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0938 AC: 14271 AN: 152120 Hom.: 1283 Cov.: 32 AF XY: 0.0970 AC XY: 7212 AN XY: 74370

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0932

Alfa AF: 0.0371 Hom.: 446

Bravo AF: 0.108

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Benign:1

protective, 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	-0.86
CADD	Benign	4.2
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9332959; hg19: chr12-16519268;