dbSNP rs4149259: EPHX2:c.*455C>T (chr8-27544977-C-T) – 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.*455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 185,498 control chromosomes in the GnomAD database, including 6,683 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 0.25 ( 6056 hom., cov: 32)

Exomes 𝑓: 0.17 ( 627 hom. )

Consequence

EPHX2
NM_001979.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

18 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6 link	c.*455C>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6 link	c.*455C>T		3_prime_UTR_variant	Exon 19 of 19	1	NM_001979.6	ENSP00000430269.1

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37561

AN:

151952

Hom.:

6036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.170

AC:

5667

AN:

33426

Hom.:

627

Cov.:

AF XY:

0.171

AC XY:

2988

AN XY:

17442

show subpopulations

African (AFR)

AF:

0.522

AC:

402

AN:

770

American (AMR)

AF:

0.138

AC:

445

AN:

3216

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

136

AN:

642

East Asian (EAS)

AF:

0.200

AC:

372

AN:

1860

South Asian (SAS)

AF:

0.186

AC:

709

AN:

3802

European-Finnish (FIN)

AF:

0.118

AC:

143

AN:

1210

Middle Eastern (MID)

AF:

0.200

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.155

AC:

3137

AN:

20230

Other (OTH)

AF:

0.190

AC:

299

AN:

1576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

216

432

649

865

1081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.247

AC:

37617

AN:

152072

Hom.:

6056

Cov.:

AF XY:

0.244

AC XY:

18103

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.460

AC:

19086

AN:

41454

American (AMR)

AF:

0.180

AC:

2747

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

701

AN:

3472

East Asian (EAS)

AF:

0.193

AC:

990

AN:

5142

South Asian (SAS)

AF:

0.199

AC:

960

AN:

4820

European-Finnish (FIN)

AF:

0.138

AC:

1462

AN:

10592

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10960

AN:

67976

Other (OTH)

AF:

0.250

AC:

529

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1327

2654

3980

5307

6634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.188

Hom.:

5457

Bravo

AF:

0.259

Asia WGS

AF:

0.212

AC:

739

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.71

(source)

DANN

Benign

0.63

PhyloP100

-1.9

Mutation Taster

=100/0

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