rs1051740

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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]

EPHX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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
EPHX1	NM_001136018.4 link	c.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
EPHX1	ENST00000272167.10 link	c.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.:

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.:

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.:

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: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

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

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

LIST_S2

Uncertain

0.95

D;.;D;D;.

MetaRNN

Benign

0.0057

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

.;L;.;L;L

PrimateAI

Uncertain

0.58

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over