dbSNP rs2292566: EPHX1:p.Lys119Lys (chr1-225831952-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001136018.4(EPHX1):c.357G>A(p.Lys119Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,702 control chromosomes in the GnomAD database, including 19,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1712 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17792 hom. )

Consequence

EPHX1
NM_001136018.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.38

Publications

39 publications found

Variant links:

Genes affected

EPHX1 (HGNC:3401): (epoxide hydrolase 1) Epoxide hydrolase is a critical biotransformation enzyme that converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body. Epoxide hydrolase functions in both the activation and detoxification of epoxides. Mutations in this gene cause preeclampsia, epoxide hydrolase deficiency or increased epoxide hydrolase activity. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2008]

EPHX1 Gene-Disease associations (from GenCC):

familial hypercholanemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

EPHX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 1-225831952-G-A is Benign according to our data. Variant chr1-225831952-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4 link	c.357G>A	p.Lys119Lys	synonymous_variant	Exon 3 of 9	ENST00000272167.10	NP_001129490.1	P07099R4SBI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10 link	c.357G>A	p.Lys119Lys	synonymous_variant	Exon 3 of 9	1	NM_001136018.4	ENSP00000272167.5		P07099

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21791

AN:

152054

Hom.:

1704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.148

GnomAD2 exomes

AF:

0.158

AC:

39728

AN:

251312

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.151

AC:

220586

AN:

1461530

Hom.:

17792

Cov.:

AF XY:

0.153

AC XY:

111289

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.132

AC:

4404

AN:

33470

American (AMR)

AF:

0.113

AC:

5034

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4981

AN:

26136

East Asian (EAS)

AF:

0.311

AC:

12329

AN:

39698

South Asian (SAS)

AF:

0.225

AC:

19419

AN:

86252

European-Finnish (FIN)

AF:

0.116

AC:

6183

AN:

53296

Middle Eastern (MID)

AF:

0.126

AC:

724

AN:

5768

European-Non Finnish (NFE)

AF:

0.143

AC:

158470

AN:

1111802

Other (OTH)

AF:

0.150

AC:

9042

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

10209

20418

30626

40835

51044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5890

11780

17670

23560

29450

<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:

0.143

AC:

21804

AN:

152172

Hom.:

1712

Cov.:

AF XY:

0.144

AC XY:

10703

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.128

AC:

5320

AN:

41518

American (AMR)

AF:

0.127

AC:

1938

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

698

AN:

3472

East Asian (EAS)

AF:

0.313

AC:

1621

AN:

5178

South Asian (SAS)

AF:

0.222

AC:

1069

AN:

4816

European-Finnish (FIN)

AF:

0.112

AC:

1186

AN:

10574

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9414

AN:

68016

Other (OTH)

AF:

0.155

AC:

328

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

969

1937

2906

3874

4843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.144

Hom.:

4831

Bravo

AF:

0.143

Asia WGS

AF:

0.267

AC:

926

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

6.1

(source)

DANN

Benign

0.67

PhyloP100

1.4

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over