chr12-16385834-T-C

Variant names:

• chr12-16385834-T-C
• rs1981752
• XM_047428856.1:c.*2246T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359720.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	ENST00000359720.3	TSL:2	n.778+2230T>C		intron	N/A
	MGST1	ENST00000538857.1	TSL:3	n.482+2230T>C		intron	N/A
	MGST1	ENST00000539036.5	TSL:4	n.400+2230T>C		intron	N/A

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

African (AFR) AF: 0.531 AC: 21992 AN: 41432

American (AMR) AF: 0.455 AC: 6941 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3464

East Asian (EAS) AF: 0.569 AC: 2927 AN: 5148

South Asian (SAS) AF: 0.404 AC: 1948 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3342 AN: 10548

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22449 AN: 67950

Other (OTH) AF: 0.420 AC: 886 AN: 2112

Alfa AF: 0.331 Hom.: 4568

Bravo AF: 0.427

Asia WGS AF: 0.532 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs1981752; hg19: chr12-16538768;