dbSNP rs2291635: EPHX2:c.1450-124G>A (chr8-27543625-G-A) – 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.1450-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 895,696 control chromosomes in the GnomAD database, including 5,844 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 0.12 ( 1172 hom., cov: 31)

Exomes 𝑓: 0.11 ( 4672 hom. )

Consequence

EPHX2
NM_001979.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

12 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6 link	c.1450-124G>A		intron_variant	Intron 16 of 18	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.1450-124G>A		intron_variant	Intron 16 of 18	1	NM_001979.6	ENSP00000430269.1		P34913-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18169

AN:

151968

Hom.:

1172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0979

GnomAD4 exome

AF:

0.107

AC:

79734

AN:

743608

Hom.:

4672

AF XY:

0.106

AC XY:

40595

AN XY:

383744

show subpopulations

African (AFR)

AF:

0.158

AC:

2986

AN:

18850

American (AMR)

AF:

0.120

AC:

3542

AN:

29546

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

657

AN:

16748

East Asian (EAS)

AF:

0.171

AC:

5948

AN:

34700

South Asian (SAS)

AF:

0.108

AC:

6164

AN:

57334

European-Finnish (FIN)

AF:

0.120

AC:

5814

AN:

48254

Middle Eastern (MID)

AF:

0.0840

AC:

353

AN:

4204

European-Non Finnish (NFE)

AF:

0.102

AC:

50610

AN:

497964

Other (OTH)

AF:

0.102

AC:

3660

AN:

36008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3616

7232

10849

14465

18081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1294

2588

3882

5176

6470

<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:

0.120

AC:

18180

AN:

152088

Hom.:

1172

Cov.:

AF XY:

0.119

AC XY:

8845

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.159

AC:

6610

AN:

41472

American (AMR)

AF:

0.101

AC:

1543

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3468

East Asian (EAS)

AF:

0.190

AC:

977

AN:

5154

South Asian (SAS)

AF:

0.120

AC:

578

AN:

4820

European-Finnish (FIN)

AF:

0.108

AC:

1143

AN:

10588

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6873

AN:

67982

Other (OTH)

AF:

0.0964

AC:

204

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

804

1608

2413

3217

4021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0920

Hom.:

960

Bravo

AF:

0.119

Asia WGS

AF:

0.144

AC:

501

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

(source)

DANN

Benign

0.65

PhyloP100

-2.1

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