Variant 8-27500979-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001979.6(EPHX2):c.155G>A(p.Arg52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 1,613,288 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 33 hom. )

Consequence

EPHX2
NM_001979.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.403

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058618486).

BP6

Variant 8-27500979-G-A is Benign according to our data. Variant chr8-27500979-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 783837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-27500979-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX2	NM_001979.6 linkuse as main transcript	c.155G>A	p.Arg52Gln	missense_variant	2/19	ENST00000521400.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX2	ENST00000521400.6 linkuse as main transcript	c.155G>A	p.Arg52Gln	missense_variant	2/19	1	NM_001979.6	P1	P34913-1

Frequencies

GnomAD3 genomes

AF:

0.00433

AC:

659

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00981

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00653

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00469

AC:

1175

AN:

250340

Hom.:

AF XY:

0.00474

AC XY:

641

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.000865

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000525

Gnomad FIN exome

AF:

0.00987

Gnomad NFE exome

AF:

0.00690

Gnomad OTH exome

AF:

0.00625

GnomAD4 exome

AF:

0.00563

AC:

8227

AN:

1461026

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

3971

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.000898

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00898

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00433

AC:

659

AN:

152262

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

305

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00981

Gnomad4 NFE

AF:

0.00653

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00583

Hom.:

Bravo

AF:

0.00401

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00500

AC:

607

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00535

EpiControl

AF:

0.00666

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	EPHX2: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.15

T;T;.;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.33

T;T;D;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.070

B;.;.;B

Vest4

0.11

MVP

0.33

MPC

0.19

ClinPred

0.0088

GERP RS

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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