rs1051740

Variant names:

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

Clinical Significance

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

Conservation

PhyloP100: 7.79

Publications

401 publications found

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 Gene-Disease associations (from GenCC):

familial hypercholanemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

EPHX1 links:

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 VariationId 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

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

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

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.:

AF XY:

0.307

AC XY:

223561

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.181

AC:

6063

AN:

33478

American (AMR)

AF:

0.382

AC:

17067

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

7593

AN:

26134

East Asian (EAS)

AF:

0.440

AC:

17463

AN:

39700

South Asian (SAS)

AF:

0.351

AC:

30247

AN:

86252

European-Finnish (FIN)

AF:

0.298

AC:

15923

AN:

53358

Middle Eastern (MID)

AF:

0.250

AC:

1442

AN:

5766

European-Non Finnish (NFE)

AF:

0.299

AC:

332978

AN:

1111816

Other (OTH)

AF:

0.308

AC:

18626

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17770

35540

53309

71079

88849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

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.:

AF XY:

0.280

AC XY:

20809

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.185

AC:

7668

AN:

41510

American (AMR)

AF:

0.328

AC:

5010

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

999

AN:

3472

East Asian (EAS)

AF:

0.449

AC:

2320

AN:

5164

South Asian (SAS)

AF:

0.366

AC:

1766

AN:

4824

European-Finnish (FIN)

AF:

0.297

AC:

3136

AN:

10566

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20451

AN:

67982

Other (OTH)

AF:

0.276

AC:

580

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1542

3083

4625

6166

7708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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) -

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

(source)

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

PhyloP100

7.8

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

Mutation Taster

=80/20

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over