rs1051740

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001136018.4(EPHX1):​c.337T>C​(p.Tyr113His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,706 control chromosomes in the GnomAD database, including 76,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6305 hom., cov: 32)
Exomes 𝑓: 0.31 ( 69953 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

4
7
7

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 7.79
Variant links:
Genes affected
EPHX1 (HGNC:3401): (epoxide hydrolase 1) Epoxide hydrolase is a critical biotransformation enzyme that converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body. Epoxide hydrolase functions in both the activation and detoxification of epoxides. Mutations in this gene cause preeclampsia, epoxide hydrolase deficiency or increased epoxide hydrolase activity. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0057053864).
BP6
Variant 1-225831932-T-C is Benign according to our data. Variant chr1-225831932-T-C is described in ClinVar as [Benign]. Clinvar id is 16604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPHX1NM_001136018.4 linkc.337T>C p.Tyr113His missense_variant Exon 3 of 9 ENST00000272167.10 NP_001129490.1 P07099R4SBI6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPHX1ENST00000272167.10 linkc.337T>C p.Tyr113His missense_variant Exon 3 of 9 1 NM_001136018.4 ENSP00000272167.5 P07099

Frequencies

GnomAD3 genomes
AF:
0.278
AC:
42243
AN:
151976
Hom.:
6297
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.184
Gnomad AMI
AF:
0.296
Gnomad AMR
AF:
0.328
Gnomad ASJ
AF:
0.288
Gnomad EAS
AF:
0.449
Gnomad SAS
AF:
0.368
Gnomad FIN
AF:
0.297
Gnomad MID
AF:
0.244
Gnomad NFE
AF:
0.301
Gnomad OTH
AF:
0.278
GnomAD2 exomes
AF:
0.321
AC:
80762
AN:
251384
AF XY:
0.321
show subpopulations
Gnomad AFR exome
AF:
0.178
Gnomad AMR exome
AF:
0.393
Gnomad ASJ exome
AF:
0.283
Gnomad EAS exome
AF:
0.461
Gnomad FIN exome
AF:
0.301
Gnomad NFE exome
AF:
0.297
Gnomad OTH exome
AF:
0.307
GnomAD4 exome
AF:
0.306
AC:
447402
AN:
1461612
Hom.:
69953
Cov.:
44
AF XY:
0.307
AC XY:
223561
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.181
AC:
6063
AN:
33478
Gnomad4 AMR exome
AF:
0.382
AC:
17067
AN:
44722
Gnomad4 ASJ exome
AF:
0.291
AC:
7593
AN:
26134
Gnomad4 EAS exome
AF:
0.440
AC:
17463
AN:
39700
Gnomad4 SAS exome
AF:
0.351
AC:
30247
AN:
86252
Gnomad4 FIN exome
AF:
0.298
AC:
15923
AN:
53358
Gnomad4 NFE exome
AF:
0.299
AC:
332978
AN:
1111816
Gnomad4 Remaining exome
AF:
0.308
AC:
18626
AN:
60386
Heterozygous variant carriers
0
17770
35540
53309
71079
88849
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
11080
22160
33240
44320
55400
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.278
AC:
42272
AN:
152094
Hom.:
6305
Cov.:
32
AF XY:
0.280
AC XY:
20809
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.185
AC:
0.184727
AN:
0.184727
Gnomad4 AMR
AF:
0.328
AC:
0.328137
AN:
0.328137
Gnomad4 ASJ
AF:
0.288
AC:
0.28773
AN:
0.28773
Gnomad4 EAS
AF:
0.449
AC:
0.449264
AN:
0.449264
Gnomad4 SAS
AF:
0.366
AC:
0.366086
AN:
0.366086
Gnomad4 FIN
AF:
0.297
AC:
0.296801
AN:
0.296801
Gnomad4 NFE
AF:
0.301
AC:
0.30083
AN:
0.30083
Gnomad4 OTH
AF:
0.276
AC:
0.275665
AN:
0.275665
Heterozygous variant carriers
0
1542
3083
4625
6166
7708
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
448
896
1344
1792
2240
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.295
Hom.:
27566
Bravo
AF:
0.276
TwinsUK
AF:
0.293
AC:
1086
ALSPAC
AF:
0.315
AC:
1215
ESP6500AA
AF:
0.176
AC:
776
ESP6500EA
AF:
0.300
AC:
2577
ExAC
AF:
0.313
AC:
38044
Asia WGS
AF:
0.394
AC:
1370
AN:
3478
EpiCase
AF:
0.302
EpiControl
AF:
0.294

ClinVar

Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Nov 10, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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) -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

EPOXIDE HYDROLASE 1 POLYMORPHISM Benign:1
Jun 01, 2001
OMIM
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Cystic fibrosis Other:1
Apr 01, 2019
Center for Computational Genomics and Data Science, University of Alabama
Significance:risk factor
Review Status:no assertion criteria provided
Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
.;T;.;T;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
D;.;D;D;.
MetaRNN
Benign
0.0057
T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.9
.;L;.;L;L
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-4.3
D;D;D;.;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.012
D;D;D;.;D
Sift4G
Pathogenic
0.0
D;D;T;D;D
Polyphen
1.0
.;D;.;D;D
Vest4
0.20, 0.38, 0.22
MPC
0.86
ClinPred
0.0077
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.75
gMVP
0.85
Mutation Taster
=80/20
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1051740; hg19: chr1-226019633; COSMIC: COSV55298811; API