12-16360227-G-C

Variant names:

• chr12-16360227-G-C
• rs4149197
• NM_020300.5:c.221+2528G>C

Variant summary

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

The NM_020300.5(MGST1):​c.221+2528G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 475,272 control chromosomes in the GnomAD database, including 103,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (28002 hom., cov: 31)
  • Exomes 𝑓: 0.68 (75877 hom.)
• Consequence: MGST1 NM_020300.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.596
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020300.5. 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_020300.5	MANE Select	c.221+2528G>C		intron	N/A	NP_064696.1	P10620-1
	MGST1	NM_001414355.1		c.236+2528G>C		intron	N/A	NP_001401284.1
	MGST1	NM_001414356.1		c.211+2538G>C		intron	N/A	NP_001401285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	ENST00000396210.8	TSL:1 MANE Select	c.221+2528G>C		intron	N/A	ENSP00000379513.3	P10620-1
	MGST1	ENST00000396207.1	TSL:1	c.221+2528G>C		intron	N/A	ENSP00000379510.1	P10620-1
	MGST1	ENST00000535309.5	TSL:1	c.221+2528G>C		intron	N/A	ENSP00000438308.1	P10620-2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89906 AN: 151846 Hom.: 27981 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.682 AC: 220492 AN: 323306 Hom.: 75877 AF XY: 0.683 AC XY: 105200 AN XY: 154052

African (AFR) AF: 0.447 AC: 2663 AN: 5954

American (AMR) AF: 0.489 AC: 173 AN: 354

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 1404 AN: 2024

East Asian (EAS) AF: 0.184 AC: 238 AN: 1292

South Asian (SAS) AF: 0.550 AC: 3509 AN: 6382

European-Finnish (FIN) AF: 0.648 AC: 70 AN: 108

Middle Eastern (MID) AF: 0.636 AC: 406 AN: 638

European-Non Finnish (NFE) AF: 0.693 AC: 205095 AN: 295862

Other (OTH) AF: 0.649 AC: 6934 AN: 10692

GnomAD4 genome AF: 0.592 AC: 89967 AN: 151966 Hom.: 28002 Cov.: 31 AF XY: 0.588 AC XY: 43630 AN XY: 74258

African (AFR) AF: 0.462 AC: 19147 AN: 41426

American (AMR) AF: 0.572 AC: 8727 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2412 AN: 3468

East Asian (EAS) AF: 0.174 AC: 898 AN: 5170

South Asian (SAS) AF: 0.533 AC: 2567 AN: 4814

European-Finnish (FIN) AF: 0.677 AC: 7126 AN: 10526

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47025 AN: 67978

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.648 Hom.: 16625

Bravo AF: 0.575

Asia WGS AF: 0.351 AC: 1222 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

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	-0.91
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4149197; hg19: chr12-16513161;