12-16385834-T-C

Position:

• chr12-16385834-T-C

Variant summary

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

The XM_047428856.1(MGST1):​c.*2246T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,948 control chromosomes in the GnomAD database, including 13,551 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 0.41 (13551 hom., cov: 31)
• Consequence: MGST1 XM_047428856.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	XM_047428856.1	c.*2246T>C		3_prime_UTR_variant	5/5		XP_047284812.1
MGST1	XM_047428857.1	c.*16+2230T>C		intron_variant			XP_047284813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000359720.3	n.778+2230T>C		intron_variant, non_coding_transcript_variant		2
MGST1	ENST00000538857.1	n.482+2230T>C		intron_variant, non_coding_transcript_variant		3
MGST1	ENST00000539036.5	n.400+2230T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62387 AN: 151830 Hom.: 13533 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.411 AC: 62438 AN: 151948 Hom.: 13551 Cov.: 31 AF XY: 0.412 AC XY: 30623 AN XY: 74264

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.420

Alfa AF: 0.327 Hom.: 3978

Bravo AF: 0.427

Asia WGS AF: 0.532 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1981752; hg19: chr12-16538768;