12-16369418-T-C

Position:

• chr12-16369418-T-C

Variant summary

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

The ENST00000535309.5(MGST1):​c.222-6704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,954 control chromosomes in the GnomAD database, including 1,856 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 0.11 (1856 hom., cov: 32)
• Consequence: MGST1 ENST00000535309.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGST1	NM_001414360.1	c.*1868T>C		3_prime_UTR_variant	4/4
MGST1	NM_001414366.1	c.*1868T>C		3_prime_UTR_variant	4/4
MGST1	XM_047428855.1	c.*1868T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGST1	ENST00000535309.5	c.222-6704T>C		intron_variant		1
MGST1	ENST00000542256.5	n.294-351T>C		intron_variant, non_coding_transcript_variant		1
MGST1	ENST00000538857.1	n.384+1953T>C		intron_variant, non_coding_transcript_variant		3
MGST1	ENST00000539036.5	n.302+11719T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16722 AN: 151836 Hom.: 1852 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.110 AC: 16746 AN: 151954 Hom.: 1856 Cov.: 32 AF XY: 0.113 AC XY: 8391 AN XY: 74294

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0494 Hom.: 103

Bravo AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10846336; hg19: chr12-16522352;