12-16365049-G-C

Variant names:

• chr12-16365049-G-C
• rs9332950
• ENST00000535309.5:c.221+7350G>C

Variant summary

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

The ENST00000535309.5(MGST1):​c.221+7350G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,084 control chromosomes in the GnomAD database, including 810 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 0.10 (810 hom., cov: 32)
• Consequence: MGST1 ENST00000535309.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST1	NM_001414360.1	c.222-2276G>C		intron_variant	Intron 3 of 3		NP_001401289.1
MGST1	NM_001414362.1	c.222-2276G>C		intron_variant	Intron 3 of 4		NP_001401291.1
MGST1	NM_001414364.1	c.222-2276G>C		intron_variant	Intron 3 of 4		NP_001401293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000535309.5	c.221+7350G>C		intron_variant	Intron 3 of 3	1		ENSP00000438308.1
MGST1	ENST00000542256.5	n.153-2276G>C		intron_variant	Intron 2 of 3	1
MGST1	ENST00000538857.1	n.244-2276G>C		intron_variant	Intron 2 of 4	3
MGST1	ENST00000539036.5	n.302+7350G>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15295 AN: 151966 Hom.: 810 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.101 AC: 15297 AN: 152084 Hom.: 810 Cov.: 32 AF XY: 0.101 AC XY: 7519 AN XY: 74348

African (AFR) AF: 0.0660 AC: 2738 AN: 41506

American (AMR) AF: 0.0858 AC: 1311 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3468

East Asian (EAS) AF: 0.164 AC: 849 AN: 5172

South Asian (SAS) AF: 0.126 AC: 606 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1171 AN: 10566

Middle Eastern (MID) AF: 0.138 AC: 40 AN: 290

European-Non Finnish (NFE) AF: 0.116 AC: 7857 AN: 67958

Other (OTH) AF: 0.105 AC: 222 AN: 2108

Alfa AF: 0.105 Hom.: 114

Bravo AF: 0.0979

Asia WGS AF: 0.144 AC: 503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.16
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: rs9332950; hg19: chr12-16517983;