12-16366329-A-G

Position:

• chr12-16366329-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001414360.1(MGST1):​c.222-996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 152,258 control chromosomes in the GnomAD database, including 19 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 0.011 (19 hom., cov: 32)
• Consequence: MGST1 NM_001414360.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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]

MGST1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1729/152258) while in subpopulation AFR AF= 0.0224 (932/41546). AF 95% confidence interval is 0.0212. There are 19 homozygotes in gnomad4. There are 830 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	NM_001414360.1	c.222-996A>G		intron_variant			NP_001401289.1
MGST1	NM_001414362.1	c.222-996A>G		intron_variant			NP_001401291.1
MGST1	NM_001414364.1	c.222-996A>G		intron_variant			NP_001401293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000535309.5	c.221+8630A>G		intron_variant		1		ENSP00000438308.1
MGST1	ENST00000542256.5	n.153-996A>G		intron_variant		1
MGST1	ENST00000538857.1	n.244-996A>G		intron_variant		3
MGST1	ENST00000539036.5	n.302+8630A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1728 AN: 152140 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00817

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0114 AC: 1729 AN: 152258 Hom.: 19 Cov.: 32 AF XY: 0.0111 AC XY: 830 AN XY: 74450

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.00818

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00653 Hom.: 0

Bravo AF: 0.0119

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9332958; hg19: chr12-16519263;