chr12-16366334-G-T

Variant names:

• chr12-16366334-G-T
• rs9332959
• ENST00000535309.5:c.221+8635G>T

Variant summary

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

The NM_001414360.1(MGST1):​c.222-991G>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 NM_001414360.1 intron
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 0.185
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414360.1. 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
	MGST1	NM_001414360.1		c.222-991G>T		intron	N/A	NP_001401289.1
	MGST1	NM_001414362.1		c.222-991G>T		intron	N/A	NP_001401291.1
	MGST1	NM_001414364.1		c.222-991G>T		intron	N/A	NP_001401293.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	ENST00000535309.5	TSL:1	c.221+8635G>T		intron	N/A	ENSP00000438308.1	P10620-2
	MGST1	ENST00000542256.5	TSL:1	n.153-991G>T		intron	N/A
	MGST1	ENST00000538857.1	TSL:3	n.244-991G>T		intron	N/A

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

African (AFR) AF: 0.202 AC: 8361 AN: 41482

American (AMR) AF: 0.143 AC: 2185 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1433 AN: 5158

South Asian (SAS) AF: 0.0968 AC: 467 AN: 4826

European-Finnish (FIN) AF: 0.0487 AC: 516 AN: 10596

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 763 AN: 68000

Other (OTH) AF: 0.0932 AC: 197 AN: 2114

Alfa AF: 0.0452 Hom.: 1768

Bravo AF: 0.108

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: protective

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9332959; hg19: chr12-16519268;