chr4-139703502-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002413.5(MGST2):ā€‹c.277T>Cā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.0055 ( 9 hom., cov: 31)
Exomes š‘“: 0.0086 ( 99 hom. )

Consequence

MGST2
NM_002413.5 missense

Scores

1
7
7

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.85
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 790448.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome 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 gnomad4_exome. There are 6570 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MGST2NM_002413.5 linkuse as main transcriptc.277T>C p.Tyr93His missense_variant 4/5 ENST00000265498.6 NP_002404.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MGST2ENST00000265498.6 linkuse as main transcriptc.277T>C p.Tyr93His missense_variant 4/51 NM_002413.5 ENSP00000265498 P1Q99735-1

Frequencies

GnomAD3 genomes
AF:
0.00553
AC:
842
AN:
152160
Hom.:
9
Cov.:
31
show subpopulations
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
GnomAD3 exomes
AF:
0.00739
AC:
1857
AN:
251402
Hom.:
17
AF XY:
0.00820
AC XY:
1114
AN XY:
135890
show subpopulations
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 SAS exome
AF:
0.0187
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00134
Gnomad4 AMR exome
AF:
0.00235
Gnomad4 ASJ exome
AF:
0.00911
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0188
Gnomad4 FIN exome
AF:
0.00509
Gnomad4 NFE exome
AF:
0.00883
Gnomad4 OTH exome
AF:
0.00831
GnomAD4 genome
AF:
0.00552
AC:
840
AN:
152278
Hom.:
9
Cov.:
31
AF XY:
0.00534
AC XY:
398
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00137
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00778
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0162
Gnomad4 FIN
AF:
0.00575
Gnomad4 NFE
AF:
0.00836
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00790
Hom.:
11
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

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 23, 2018- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster
Benign
1.0
D;N
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs116372322; hg19: chr4-140624656; COSMIC: COSV99643690; COSMIC: COSV99643690; API