1-165652970-C-T

Variant names:

• chr1-165652970-C-T
• rs2297765
• NM_004528.4:c.249+935C>T

Variant summary

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

The NM_004528.4(MGST3):​c.249+935C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,038 control chromosomes in the GnomAD database, including 17,742 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 0.46 (17742 hom., cov: 33)
• Consequence: MGST3 NM_004528.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST3	NM_004528.4	MANE Select	c.249+935C>T		intron	N/A	NP_004519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST3	ENST00000367889.8	TSL:1 MANE Select	c.249+935C>T		intron	N/A	ENSP00000356864.3
	MGST3	ENST00000367883.3	TSL:3	c.291+935C>T		intron	N/A	ENSP00000356858.1
	MGST3	ENST00000367885.5	TSL:2	c.291+935C>T		intron	N/A	ENSP00000356860.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70438 AN: 151918 Hom.: 17706 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.464 AC: 70530 AN: 152038 Hom.: 17742 Cov.: 33 AF XY: 0.462 AC XY: 34308 AN XY: 74340

African (AFR) AF: 0.659 AC: 27306 AN: 41456

American (AMR) AF: 0.385 AC: 5887 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3468

East Asian (EAS) AF: 0.178 AC: 923 AN: 5182

South Asian (SAS) AF: 0.447 AC: 2152 AN: 4818

European-Finnish (FIN) AF: 0.380 AC: 4023 AN: 10582

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26609 AN: 67948

Other (OTH) AF: 0.461 AC: 969 AN: 2104

Alfa AF: 0.355 Hom.: 3264

Bravo AF: 0.472

Asia WGS AF: 0.369 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.047
DANN	Benign	0.21
PhyloP100		-2.8
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: rs2297765; hg19: chr1-165622207;