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rs1051740

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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
5

Clinical Significance

Benign criteria provided, single submitter B:2O: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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons MANE UniProt
EPHX1NM_001136018.4 linkuse as main transcriptc.337T>C p.Tyr113His missense_variant 3/9 ENST00000272167.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPHX1ENST00000272167.10 linkuse as main transcriptc.337T>C p.Tyr113His missense_variant 3/91 NM_001136018.4 P1

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
GnomAD3 exomes
AF:
0.321
AC:
80762
AN:
251384
Hom.:
13625
AF XY:
0.321
AC XY:
43628
AN XY:
135882
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 SAS exome
AF:
0.352
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
Gnomad4 AMR exome
AF:
0.382
Gnomad4 ASJ exome
AF:
0.291
Gnomad4 EAS exome
AF:
0.440
Gnomad4 SAS exome
AF:
0.351
Gnomad4 FIN exome
AF:
0.298
Gnomad4 NFE exome
AF:
0.299
Gnomad4 OTH exome
AF:
0.308
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
Gnomad4 AMR
AF:
0.328
Gnomad4 ASJ
AF:
0.288
Gnomad4 EAS
AF:
0.449
Gnomad4 SAS
AF:
0.366
Gnomad4 FIN
AF:
0.297
Gnomad4 NFE
AF:
0.301
Gnomad4 OTH
AF:
0.276
Alfa
AF:
0.295
Hom.:
12549
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:2Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

EPOXIDE HYDROLASE 1 POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMJun 01, 2001- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018This variant is associated with the following publications: (PMID: 23580125, 7516776, 15061915, 15355699, 22206016, 23451147, 21445251, 19952982, 8944076, 20932192, 15535985, 22610071, 19307236, 21649467, 18439551, 25087612) -
Cystic fibrosis Other:1
risk factor, no assertion criteria providedresearchCenter for Computational Genomics and Data Science, University of AlabamaApr 01, 2019- -

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
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
MutationTaster
Benign
9.7e-7
P;P
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

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