dbSNP rs1126452: EPHX2:p.Pro531Pro (chr8-27544447-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001979.6(EPHX2):c.1593A>C(p.Pro531Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,310 control chromosomes in the GnomAD database, including 75,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 13745 hom., cov: 31)

Exomes 𝑓: 0.28 ( 62164 hom. )

Consequence

EPHX2
NM_001979.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

Publications

41 publications found

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 Gene-Disease associations (from GenCC):

hypercholesterolemia, familial, 1
Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

EPHX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6 link	c.1593A>C	p.Pro531Pro	synonymous_variant	Exon 19 of 19	ENST00000521400.6	NP_001970.2	P34913-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6 link	c.1593A>C	p.Pro531Pro	synonymous_variant	Exon 19 of 19	1	NM_001979.6	ENSP00000430269.1		P34913-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58130

AN:

151820

Hom.:

13722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.299

AC:

74751

AN:

249976

AF XY:

0.289

show subpopulations

Gnomad AFR exome

AF:

0.683

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.282

AC:

412691

AN:

1461372

Hom.:

62164

Cov.:

AF XY:

0.280

AC XY:

203837

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.687

AC:

22974

AN:

33462

American (AMR)

AF:

0.270

AC:

12078

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

6452

AN:

26136

East Asian (EAS)

AF:

0.418

AC:

16595

AN:

39692

South Asian (SAS)

AF:

0.286

AC:

24635

AN:

86240

European-Finnish (FIN)

AF:

0.262

AC:

14002

AN:

53420

Middle Eastern (MID)

AF:

0.287

AC:

1642

AN:

5716

European-Non Finnish (NFE)

AF:

0.266

AC:

296173

AN:

1111606

Other (OTH)

AF:

0.300

AC:

18140

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14970

29941

44911

59882

74852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10246

20492

30738

40984

51230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58197

AN:

151938

Hom.:

13745

Cov.:

AF XY:

0.378

AC XY:

28099

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.671

AC:

27768

AN:

41402

American (AMR)

AF:

0.290

AC:

4435

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

822

AN:

3464

East Asian (EAS)

AF:

0.390

AC:

2007

AN:

5144

South Asian (SAS)

AF:

0.318

AC:

1527

AN:

4806

European-Finnish (FIN)

AF:

0.253

AC:

2678

AN:

10572

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17895

AN:

67966

Other (OTH)

AF:

0.357

AC:

751

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1589

3178

4766

6355

7944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.299

Hom.:

27056

Bravo

AF:

0.396

Asia WGS

AF:

0.358

AC:

1249

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.33

(source)

DANN

Benign

0.42

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over