12-16487298-C-T

Variant names:

• chr12-16487298-C-T
• rs721602
• ENST00000538857.1:n.483-102230C>T

Variant summary

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

The ENST00000538857.1(MGST1):​n.483-102230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,984 control chromosomes in the GnomAD database, including 17,895 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 0.47 (17895 hom., cov: 32)
• Consequence: MGST1 ENST00000538857.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST1	XM_047428857.1	c.*17-102230C>T		intron_variant	Intron 5 of 5		XP_047284813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000538857.1	n.483-102230C>T		intron_variant	Intron 4 of 4	3
MGST1	ENST00000539036.5	n.400+103694C>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71330 AN: 151866 Hom.: 17889 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.469 AC: 71348 AN: 151984 Hom.: 17895 Cov.: 32 AF XY: 0.463 AC XY: 34420 AN XY: 74288

African (AFR) AF: 0.274 AC: 11377 AN: 41464

American (AMR) AF: 0.487 AC: 7439 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2212 AN: 5166

South Asian (SAS) AF: 0.501 AC: 2411 AN: 4814

European-Finnish (FIN) AF: 0.509 AC: 5375 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39257 AN: 67958

Other (OTH) AF: 0.471 AC: 989 AN: 2098

Alfa AF: 0.512 Hom.: 2523

Bravo AF: 0.457

Asia WGS AF: 0.431 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.23
PhyloP100		-0.029

Splicing

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

Other links and lift over

dbSNP: rs721602; hg19: chr12-16640232;