ClinVar Genomic variation as it relates to human health
NM_001136018.4(EPHX1):c.337T>C (p.Tyr113His)
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001136018.4(EPHX1):c.337T>C (p.Tyr113His)
Variation ID: 16604 Accession: VCV000016604.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q42.12 1: 225831932 (GRCh38) [ NCBI UCSC ] 1: 226019633 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 22, 2016 Sep 29, 2024 Nov 10, 2018 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001136018.4:c.337T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001129490.1:p.Tyr113His missense NM_000120.4:c.337T>C NP_000111.1:p.Tyr113His missense NM_001291163.2:c.337T>C NP_001278092.1:p.Tyr113His missense NM_001378426.1:c.337T>C NP_001365355.1:p.Tyr113His missense NM_001378427.1:c.337T>C NP_001365356.1:p.Tyr113His missense NM_001378428.1:c.310T>C NP_001365357.1:p.Tyr104His missense NM_001378429.1:c.337T>C NP_001365358.1:p.Tyr113His missense NM_001378430.1:c.337T>C NP_001365359.1:p.Tyr113His missense NM_001378431.1:c.337T>C NP_001365360.1:p.Tyr113His missense NM_001378432.1:c.337T>C NP_001365361.1:p.Tyr113His missense NR_165625.1:n.388T>C non-coding transcript variant NR_165626.1:n.834T>C non-coding transcript variant NR_165627.1:n.533T>C non-coding transcript variant NC_000001.11:g.225831932T>C NC_000001.10:g.226019633T>C NG_009776.1:g.26837T>C P07099:p.Tyr113His - Protein change
- Y113H, Y104H
- Other names
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- Canonical SPDI
- NC_000001.11:225831931:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.31330 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.27126
Trans-Omics for Precision Medicine (TOPMed) 0.27601
1000 Genomes Project 30x 0.31168
1000 Genomes Project 0.31330
Exome Aggregation Consortium (ExAC) 0.31338
The Genome Aggregation Database (gnomAD), exomes 0.32127
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| EPHX1 | - | - |
GRCh38 GRCh37 |
61 | 128 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
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EPOXIDE HYDROLASE 1 POLYMORPHISM
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Benign (1) |
no assertion criteria provided
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Jun 1, 2001 | RCV000018075.17 |
| risk factor (1) |
no assertion criteria provided
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Apr 1, 2019 | RCV000991132.10 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 10, 2018 | RCV001610293.12 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Benign
(Nov 10, 2018)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001841478.1
First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 23580125, 7516776, 15061915, 15355699, 22206016, 23451147, 21445251, 19952982, 8944076, 20932192, 15535985, 22610071, 19307236, 21649467, 18439551, 25087612)
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Benign
(-)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: not provided
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005281279.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(Jun 01, 2001)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - EPOXIDE HYDROLASE 1 POLYMORPHISM
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000038354.7
First in ClinVar: Apr 04, 2013 Last updated: Feb 20, 2022 |
Comment on evidence:
This variant, formerly titled LYMPHOPROLIFERATIVE DISORDERS, SUSCEPTIBILITY TO, with the following included titles, PREECLAMPSIA, SUSCEPTIBILITY TO; EMPHYSEMA, SUSCEPTIBILITY TO; and PULMONARY DISEASE, CHRONIC OBSTRUCTIVE, SUSCEPTIBILITY … (more)
This variant, formerly titled LYMPHOPROLIFERATIVE DISORDERS, SUSCEPTIBILITY TO, with the following included titles, PREECLAMPSIA, SUSCEPTIBILITY TO; EMPHYSEMA, SUSCEPTIBILITY TO; and PULMONARY DISEASE, CHRONIC OBSTRUCTIVE, SUSCEPTIBILITY TO, has been reclassified as a polymorphism because in the ExAC database (September 20, 2017) the variant was present in 38,033 of 121,362 alleles, including 6,357 homozygotes (Hamosh, 2017). Hassett et al. (1994) described a correlation between mutant alleles of EPHX and diminished enzymatic activity. They demonstrated by in vitro expression studies of cDNA that substitution of his113 for the more commonly occurring tyr113 residue in exon 3 decreased EPHX activity approximately 40%. Variation of this type may be responsible for genetic susceptibility to the environmental carcinogen aflatoxin B1 (McGlynn et al., 1995), and explained variation in the frequency of hepatocellular carcinoma (HCC; 114550). Sarmanova et al. (2001) determined the frequency of polymorphisms in several biotransformation enzymes in patients with morbus Hodgkin and non-Hodgkin lymphomas (NHL; 605027) and age- and sex-matched healthy individuals. The distribution of genotypes in CYP2E1-intron 6 (124040.0002) was significantly different between the control group and all lymphomas (P = 0.03), patients with NHL (P = 0.024), and especially aggressive diffuse NHL (P = 0.007). The EPHX-exon 3 genotype distribution was significantly different between control males and males with all lymphomas (P = 0.01) or with NHL (P = 0.019). The authors suggested that genetic polymorphisms of biotransformation enzymes may play a significant role in the development of lymphoid malignancies. Zusterzeel et al. (2001) studied genetic variability of the EPHX1 gene in women with a history of preeclampsia (189800). They found a significantly higher frequency of the high activity tyr113/tyr113 genotype (odds ratio 2.0, 95% C.I. 1.2-3.7) in women with a history of preeclampsia compared to controls. Smith and Harrison (1997) studied EPHX1 polymorphisms in patients with various pulmonary diseases and found that the very slow phenotype (his113) was 4 to 5 times more common in patients with COPD or emphysema compared to controls. (less)
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risk factor
(Apr 01, 2019)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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Center for Computational Genomics and Data Science, University of Alabama
Accession: SCV001142519.1
First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
Number of individuals with the variant: 3
Indication for testing: Cystic fibrosis
Zygosity: Single Heterozygote
Secondary finding: no
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Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Applying whole-genome sequencing in relation to phenotype and outcomes in siblings with cystic fibrosis. | Wilk MA | Cold Spring Harbor molecular case studies | 2020 | PMID: 32014855 |
| Microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease: A comprehensive meta-analysis. | Li H | Oncology letters | 2013 | PMID: 23426996 |
| Genetic associations with hypoxemia and pulmonary arterial pressure in COPD. | Castaldi PJ | Chest | 2009 | PMID: 19017876 |
| Genetic polymorphisms of GSTP1 and mEPHX correlate with oxidative stress markers and lung function in COPD. | Vibhuti A | Biochemical and biophysical research communications | 2007 | PMID: 17532303 |
| Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. | Carlton VE | Nature genetics | 2003 | PMID: 12704386 |
| Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas. | Sarmanová J | Human molecular genetics | 2001 | PMID: 11406608 |
| A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia. | Zusterzeel PL | Journal of medical genetics | 2001 | PMID: 11283205 |
| Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. | Smith CA | Lancet (London, England) | 1997 | PMID: 9288046 |
| Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. | McGlynn KA | Proceedings of the National Academy of Sciences of the United States of America | 1995 | PMID: 7892276 |
| Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. | Hassett C | Human molecular genetics | 1994 | PMID: 7516776 |
| Hamosh, A. Personal Communication. 2017. Baltimore, Md. | - | - | - | - |
| click to load more citations click to collapse | ||||
Text-mined citations for rs1051740 ...
HelpRecord last updated Jan 13, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.