rs11799886

Variant names:

• chr1-165651555-G-A
• rs11799886
• NM_004528.4:c.192-423G>A

Variant summary

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

The NM_004528.4(MGST3):​c.192-423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 297,952 control chromosomes in the GnomAD database, including 3,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (1864 hom., cov: 31)
  • Exomes 𝑓: 0.14 (1692 hom.)
• Consequence: MGST3 NM_004528.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.81
• Publications: 10 publications found

Genes affected

MGST3 (HGNC:7064): (microsomal glutathione S-transferase 3) This gene encodes a member of the MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) protein family. Members of this family are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes an enzyme which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. This enzyme also demonstrates glutathione-dependent peroxidase activity towards lipid hydroperoxides.[provided by RefSeq, May 2011]

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 = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004528.4. 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
	MGST3	NM_004528.4	MANE Select	c.192-423G>A		intron	N/A	NP_004519.1	O14880

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST3	ENST00000367889.8	TSL:1 MANE Select	c.192-423G>A		intron	N/A	ENSP00000356864.3	O14880
	MGST3	ENST00000367883.3	TSL:3	c.234-423G>A		intron	N/A	ENSP00000356858.1	Q5VV89
	MGST3	ENST00000367885.5	TSL:2	c.234-423G>A		intron	N/A	ENSP00000356860.1	Q5VV89

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22437 AN: 151958 Hom.: 1860 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.138 AC: 20190 AN: 145876 Hom.: 1692 Cov.: 0 AF XY: 0.131 AC XY: 10298 AN XY: 78576

African (AFR) AF: 0.142 AC: 636 AN: 4478

American (AMR) AF: 0.0916 AC: 471 AN: 5142

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 254 AN: 3576

East Asian (EAS) AF: 0.0164 AC: 100 AN: 6080

South Asian (SAS) AF: 0.0654 AC: 1592 AN: 24334

European-Finnish (FIN) AF: 0.164 AC: 1101 AN: 6728

Middle Eastern (MID) AF: 0.125 AC: 70 AN: 560

European-Non Finnish (NFE) AF: 0.170 AC: 14894 AN: 87584

Other (OTH) AF: 0.145 AC: 1072 AN: 7394

GnomAD4 genome AF: 0.148 AC: 22445 AN: 152076 Hom.: 1864 Cov.: 31 AF XY: 0.142 AC XY: 10575 AN XY: 74344

African (AFR) AF: 0.147 AC: 6080 AN: 41464

American (AMR) AF: 0.116 AC: 1778 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5174

South Asian (SAS) AF: 0.0548 AC: 264 AN: 4816

European-Finnish (FIN) AF: 0.158 AC: 1675 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11833 AN: 67976

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.162 Hom.: 8095

Bravo AF: 0.145

Asia WGS AF: 0.0500 AC: 174 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	0.48
DANN	Benign	0.43
PhyloP100		-1.8
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: rs11799886; hg19: chr1-165620792;