dbSNP rs1042032: EPHX2:c.*35A>G (chr8-27544557-A-G) – 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.*35A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,607,632 control chromosomes in the GnomAD database, including 75,683 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 ( 13790 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61893 hom. )

Consequence

EPHX2
NM_001979.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.222

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6 link	c.*35A>G		3_prime_UTR_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.*35A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_001979.6	ENSP00000430269.1		P34913-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58250

AN:

152010

Hom.:

13767

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:

0.392

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.363

GnomAD2 exomes

AF:

0.299

AC:

75005

AN:

250930

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:

0.283

AC:

411295

AN:

1455504

Hom.:

61893

Cov.:

AF XY:

0.281

AC XY:

203216

AN XY:

724388

show subpopulations

African (AFR)

AF:

0.687

AC:

22922

AN:

33376

American (AMR)

AF:

0.270

AC:

12075

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

6444

AN:

26112

East Asian (EAS)

AF:

0.417

AC:

16558

AN:

39668

South Asian (SAS)

AF:

0.286

AC:

24629

AN:

86092

European-Finnish (FIN)

AF:

0.262

AC:

13995

AN:

53408

Middle Eastern (MID)

AF:

0.272

AC:

1263

AN:

4640

European-Non Finnish (NFE)

AF:

0.267

AC:

295359

AN:

1107408

Other (OTH)

AF:

0.300

AC:

18050

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

15195

30391

45586

60782

75977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10204

20408

30612

40816

51020

<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:

58317

AN:

152128

Hom.:

13790

Cov.:

AF XY:

0.378

AC XY:

28137

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.671

AC:

27844

AN:

41484

American (AMR)

AF:

0.291

AC:

4442

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

823

AN:

3472

East Asian (EAS)

AF:

0.392

AC:

2018

AN:

5154

South Asian (SAS)

AF:

0.318

AC:

1533

AN:

4826

European-Finnish (FIN)

AF:

0.253

AC:

2680

AN:

10580

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17906

AN:

68006

Other (OTH)

AF:

0.358

AC:

757

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1601

3202

4802

6403

8004

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:

0.298

Hom.:

13727

Bravo

AF:

0.396

Asia WGS

AF:

0.359

AC:

1251

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.14

(source)

DANN

Benign

0.34

PhyloP100

-0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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