Variant rs41507953 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001979.6(EPHX2):c.164A>G(p.Lys55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,612,256 control chromosomes in the GnomAD database, including 10,110 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1480 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8630 hom. )

Consequence

EPHX2
NM_001979.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.28

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013301373).

BP6

Variant 8-27500988-A-G is Benign according to our data. Variant chr8-27500988-A-G is described in ClinVar as [Benign]. Clinvar id is 3059509.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX2	NM_001979.6 linkuse as main transcript	c.164A>G	p.Lys55Arg	missense_variant	2/19	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6 linkuse as main transcript	c.164A>G	p.Lys55Arg	missense_variant	2/19	1	NM_001979.6	ENSP00000430269	P1	P34913-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19571

AN:

152064

Hom.:

1465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0925

Gnomad ASJ

AF:

0.0839

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0646

Gnomad FIN

AF:

0.0855

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.0868

AC:

21707

AN:

249942

Hom.:

1237

AF XY:

0.0862

AC XY:

11654

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0504

Gnomad ASJ exome

AF:

0.0819

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0613

Gnomad FIN exome

AF:

0.0823

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0942

GnomAD4 exome

AF:

0.102

AC:

149556

AN:

1460074

Hom.:

8630

Cov.:

AF XY:

0.101

AC XY:

73459

AN XY:

726392

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0550

Gnomad4 ASJ exome

AF:

0.0809

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.0806

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.129

AC:

19621

AN:

152182

Hom.:

1480

Cov.:

AF XY:

0.126

AC XY:

9366

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0924

Gnomad4 ASJ

AF:

0.0839

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0639

Gnomad4 FIN

AF:

0.0855

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.105

Hom.:

1771

Bravo

AF:

0.134

TwinsUK

AF:

0.122

AC:

453

ALSPAC

AF:

0.107

AC:

413

ESP6500AA

AF:

0.218

AC:

959

ESP6500EA

AF:

0.104

AC:

895

ExAC

AF:

0.0899

AC:

10920

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EPHX2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.035

DANN

Benign

0.29

DEOGEN2

Benign

0.065

T;T;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.28

T;T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.82

N;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.49

N;N;N;N;N

REVEL

Benign

0.028

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;.;.;B

Vest4

0.096

MPC

0.070

ClinPred

0.00030

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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