Variant 1-225838705-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136018.4(EPHX1):c.416A>T(p.His139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H139R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

EPHX1 (HGNC:):

EPHX1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045999378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.416A>T	p.His139Leu	missense_variant	4/9	ENST00000272167.10	NP_001129490.1	P07099R4SBI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.416A>T	p.His139Leu	missense_variant	4/9	1	NM_001136018.4	ENSP00000272167.5	P07099
EPHX1	ENST00000366837.5 linkuse as main transcript	c.416A>T	p.His139Leu	missense_variant	4/9	1		ENSP00000355802.4	P07099
EPHX1	ENST00000614058.4 linkuse as main transcript	c.416A>T	p.His139Leu	missense_variant	4/9	1		ENSP00000480004.1	P07099
EPHX1	ENST00000448202.5 linkuse as main transcript	c.*8A>T		downstream_gene_variant		2		ENSP00000408469.1	B1AQP8

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251356

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.6

DANN

Benign

0.66

DEOGEN2

Benign

0.067

.;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.17

T;.;T;.

M_CAP

Benign

0.0096

MetaRNN

Benign

0.046

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.14

.;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.2

N;N;.;N

REVEL

Benign

0.016

Sift

Benign

0.71

T;T;.;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.0050

.;B;B;B

Vest4

0.20, 0.14, 0.19

MutPred

0.37

Loss of disorder (P = 0.0361);Loss of disorder (P = 0.0361);Loss of disorder (P = 0.0361);Loss of disorder (P = 0.0361);

MVP

0.23

MPC

0.24

ClinPred

0.011

GERP RS

2.5

Varity_R

0.028

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over