Variant 1-225831807-G-A 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.212G>A(p.Arg71His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,078 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 10 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.71

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=0.0066372156).

BP6

Variant 1-225831807-G-A is Benign according to our data. Variant chr1-225831807-G-A is described in ClinVar as [Benign]. Clinvar id is 709591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00535 (815/152202) while in subpopulation AFR AF= 0.019 (787/41530). AF 95% confidence interval is 0.0179. There are 11 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.212G>A	p.Arg71His	missense_variant	3/9	ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.212G>A	p.Arg71His	missense_variant	3/9	1	NM_001136018.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

813

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.000118

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.00143

AC:

359

AN:

251488

Hom.:

AF XY:

0.00116

AC XY:

158

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000610

AC:

892

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

380

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00535

AC:

815

AN:

152202

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

378

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00613

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00170

AC:

206

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

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

Invitae

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;.;D;D;.

MetaRNN

Benign

0.0066

T;T;T;T;T

MetaSVM

Benign

-0.70

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.5

D;D;D;.;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.010

D;D;D;.;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

1.0

.;D;.;D;D

Vest4

0.84, 0.78

MVP

0.81

MPC

0.85

ClinPred

0.11

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.84

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