rs2234922

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001136018.4(EPHX1):c.416A>G(p.His139Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,613,876 control chromosomes in the GnomAD database, including 34,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4315 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29892 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.840

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=0.0043976605).

BP6

Variant 1-225838705-A-G is Benign according to our data. Variant chr1-225838705-A-G is described in ClinVar as [Benign]. Clinvar id is 16605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-225838705-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.416A>G	p.His139Arg	missense_variant	4/9	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EPHX1	ENST00000272167.10 linkuse as main transcript	c.416A>G	p.His139Arg	missense_variant	4/9	1	NM_001136018.4	ENSP00000272167	P1
EPHX1	ENST00000366837.5 linkuse as main transcript	c.416A>G	p.His139Arg	missense_variant	4/9	1		ENSP00000355802	P1
EPHX1	ENST00000614058.4 linkuse as main transcript	c.416A>G	p.His139Arg	missense_variant	4/9	1		ENSP00000480004	P1
EPHX1	ENST00000448202.5 linkuse as main transcript			downstream_gene_variant		2		ENSP00000408469

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34379

AN:

151902

Hom.:

4306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.187

AC:

47000

AN:

251356

Hom.:

4990

AF XY:

0.191

AC XY:

25898

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.0937

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.198

AC:

289533

AN:

1461856

Hom.:

29892

Cov.:

AF XY:

0.199

AC XY:

144857

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.0992

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.226

AC:

34426

AN:

152020

Hom.:

4315

Cov.:

AF XY:

0.221

AC XY:

16463

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.193

Hom.:

7043

Bravo

AF:

0.229

TwinsUK

AF:

0.200

AC:

742

ALSPAC

AF:

0.202

AC:

779

ESP6500AA

AF:

0.337

AC:

1484

ESP6500EA

AF:

0.205

AC:

1763

ExAC

AF:

0.196

AC:

23815

EpiCase

AF:

0.191

EpiControl

AF:

0.191

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	This variant is associated with the following publications: (PMID: 25087612, 19307236, 15535985, 21183608, 20091863, 18571762, 19952982, 21445251, 22928041, 23451147, 12173035, 20157331) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

EPOXIDE HYDROLASE 1 POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Sep 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.9

DANN

Benign

0.49

DEOGEN2

Benign

0.033

.;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.022

T;.;T;.

MetaRNN

Benign

0.0044

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;N;N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

0.76

N;N;.;N

REVEL

Benign

0.028

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.0

.;B;B;B

Vest4

0.011, 0.018, 0.012

MPC

0.24

ClinPred

0.00065

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.32

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