Variant rs751141 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001979.6(EPHX2):c.860G>A(p.Arg287Gln) variant causes a missense change. The variant allele was found at a frequency of 0.108 in 1,613,354 control chromosomes in the GnomAD database, including 10,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R287W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.10 ( 917 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9234 hom. )

Consequence

EPHX2
NM_001979.6 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 7.19

Variant links:

Genes affected

EPHX2 (HGNC:3402): (epoxide hydrolase 2) This gene encodes a member of the epoxide hydrolase family. The protein, found in both the cytosol and peroxisomes, binds to specific epoxides and converts them to the corresponding dihydrodiols. Mutations in this gene have been associated with familial hypercholesterolemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

EPHX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024335682).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX2	NM_001979.6 linkuse as main transcript	c.860G>A	p.Arg287Gln	missense_variant	8/19	ENST00000521400.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX2	ENST00000521400.6 linkuse as main transcript	c.860G>A	p.Arg287Gln	missense_variant	8/19	1	NM_001979.6	P1	P34913-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15880

AN:

151900

Hom.:

918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0939

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0890

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.117

AC:

29461

AN:

251406

Hom.:

2087

AF XY:

0.113

AC XY:

15371

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0890

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.0662

Gnomad EAS exome

AF:

0.215

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0987

Gnomad NFE exome

AF:

0.0978

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.109

AC:

158952

AN:

1461336

Hom.:

9234

Cov.:

AF XY:

0.108

AC XY:

78254

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.0680

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.105

AC:

15889

AN:

152018

Hom.:

917

Cov.:

AF XY:

0.105

AC XY:

7774

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0939

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0646

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0890

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.0999

Alfa

AF:

0.102

Hom.:

1997

Bravo

AF:

0.106

TwinsUK

AF:

0.0987

AC:

366

ALSPAC

AF:

0.106

AC:

408

ESP6500AA

AF:

0.0937

AC:

413

ESP6500EA

AF:

0.107

AC:

916

ExAC

AF:

0.115

AC:

14003

Asia WGS

AF:

0.152

AC:

529

AN:

3478

EpiCase

AF:

0.0935

EpiControl

AF:

0.0886

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 27, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.050

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.33

T;.;.;.;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D;D;D;D

MetaRNN

Benign

0.0024

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.;.;.

MutationTaster

Benign

4.2e-8

P;P;P;P;P

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0080

D;D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;D;D

Polyphen

1.0

D;.;.;.;D

Vest4

0.61

MPC

0.37

ClinPred

0.0096

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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