4-139703502-T-C

Variant names:

• chr4-139703502-T-C
• rs116372322
• NM_002413.5:c.277T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002413.5(MGST2):​c.277T>C​(p.Tyr93His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00834 in 1,614,028 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0086 (99 hom.)
• Consequence: MGST2 NM_002413.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.85
• Publications: 12 publications found

Genes affected

MGST2 (HGNC:7063): (microsomal glutathione S-transferase 2) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes a protein which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007955819).
• BP6: Variant 4-139703502-T-C is Benign according to our data. Variant chr4-139703502-T-C is described in ClinVar as Benign. ClinVar VariationId is 790448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00864 (12626/1461750) while in subpopulation SAS AF = 0.0188 (1618/86256). AF 95% confidence interval is 0.018. There are 99 homozygotes in GnomAdExome4. There are 6570 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002413.5. 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
	MGST2	NM_002413.5	MANE Select	c.277T>C	p.Tyr93His	missense	Exon 4 of 5	NP_002404.1	Q99735-1
	MGST2	NM_001204366.2		c.277T>C	p.Tyr93His	missense	Exon 4 of 6	NP_001191295.1	Q99735-1
	MGST2	NM_001204367.2		c.73T>C	p.Tyr25His	missense	Exon 3 of 5	NP_001191296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST2	ENST00000265498.6	TSL:1 MANE Select	c.277T>C	p.Tyr93His	missense	Exon 4 of 5	ENSP00000265498.1	Q99735-1
	MGST2	ENST00000515137.5	TSL:1	n.264T>C		non_coding_transcript_exon	Exon 3 of 5
	MGST2	ENST00000899649.1		c.370T>C	p.Tyr124His	missense	Exon 5 of 6	ENSP00000569708.1

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 842 AN: 152160 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.00575

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00836

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00739 AC: 1857 AN: 251402 AF XY: 0.00820

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00853

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00564

Gnomad NFE exome AF: 0.00830

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00864 AC: 12626 AN: 1461750 Hom.: 99 Cov.: 31 AF XY: 0.00903 AC XY: 6570 AN XY: 727176

African (AFR) AF: 0.00134 AC: 45 AN: 33480

American (AMR) AF: 0.00235 AC: 105 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00911 AC: 238 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0188 AC: 1618 AN: 86256

European-Finnish (FIN) AF: 0.00509 AC: 272 AN: 53414

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5764

European-Non Finnish (NFE) AF: 0.00883 AC: 9818 AN: 1111914

Other (OTH) AF: 0.00831 AC: 502 AN: 60382

GnomAD4 genome AF: 0.00552 AC: 840 AN: 152278 Hom.: 9 Cov.: 31 AF XY: 0.00534 AC XY: 398 AN XY: 74464

African (AFR) AF: 0.00137 AC: 57 AN: 41552

American (AMR) AF: 0.00235 AC: 36 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4818

European-Finnish (FIN) AF: 0.00575 AC: 61 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00836 AC: 569 AN: 68026

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00765 Hom.: 22

Bravo AF: 0.00481

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00837 AC: 72

ExAC AF: 0.00821 AC: 997

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00829

EpiControl AF: 0.00735

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0080	T
MetaSVM	Uncertain	0.038	D
PhyloP100		2.8
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.095
Sift	Benign	0.061	T
Sift4G	Benign	0.22	T
Vest4		0.39
MVP		0.72
ClinPred		0.040	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.84
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs116372322; hg19: chr4-140624656; COSMIC: COSV99643690; COSMIC: COSV99643690;