Variant 1-225828874-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001136018.4(EPHX1):c.145C>T(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,600,110 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0058 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00056 ( 8 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.763

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0116193).

BP6

Variant 1-225828874-C-T is Benign according to our data. Variant chr1-225828874-C-T is described in ClinVar as [Benign]. Clinvar id is 786997.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00582 (881/151370) while in subpopulation AFR AF= 0.0204 (839/41170). AF 95% confidence interval is 0.0192. There are 10 homozygotes in gnomad4. There are 408 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	2/9	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	2/9	1	NM_001136018.4	ENSP00000272167	P1

Frequencies

GnomAD3 genomes

AF:

0.00580

AC:

877

AN:

151246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00211

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00338

GnomAD3 exomes

AF:

0.00144

AC:

326

AN:

226284

Hom.:

AF XY:

0.00107

AC XY:

130

AN XY:

122046

show subpopulations

Gnomad AFR exome

AF:

0.0190

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000608

Gnomad OTH exome

AF:

0.000707

GnomAD4 exome

AF:

0.000565

AC:

818

AN:

1448740

Hom.:

Cov.:

AF XY:

0.000495

AC XY:

356

AN XY:

719386

show subpopulations

Gnomad4 AFR exome

AF:

0.0193

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000254

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00582

AC:

881

AN:

151370

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

408

AN XY:

73936

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.00211

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.000941

Hom.:

Bravo

AF:

0.00662

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00160

AC:

194

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

.;T;.;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;.;D;D;.

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.5

.;H;.;H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-5.4

D;D;D;.;D

REVEL

Benign

0.22

Sift

Uncertain

0.0050

D;D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

0.99

.;D;.;D;D

Vest4

0.20, 0.20

MVP

0.50

MPC

0.29

ClinPred

0.051

GERP RS

5.0

Varity_R

0.37

gMVP

0.67

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