Variant chr1-225839847-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001136018.4(EPHX1):c.741C>T(p.His247His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 1,613,916 control chromosomes in the GnomAD database, including 3,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 240 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2944 hom. )

Consequence

EPHX1
NM_001136018.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.763

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-225839847-C-T is Benign according to our data. Variant chr1-225839847-C-T is described in ClinVar as [Benign]. Clinvar id is 1251795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4 link	c.741C>T	p.His247His	synonymous_variant	Exon 6 of 9	ENST00000272167.10	NP_001129490.1	P07099R4SBI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPHX1	ENST00000272167.10 link	c.741C>T	p.His247His	synonymous_variant	Exon 6 of 9	1	NM_001136018.4	ENSP00000272167.5	P07099
EPHX1	ENST00000366837.5 link	c.741C>T	p.His247His	synonymous_variant	Exon 6 of 9	1		ENSP00000355802.4	P07099
EPHX1	ENST00000614058.4 link	c.741C>T	p.His247His	synonymous_variant	Exon 6 of 9	1		ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8112

AN:

152184

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0334

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0523

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.0755

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0524

AC:

13171

AN:

251364

Hom.:

415

AF XY:

0.0533

AC XY:

7235

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.0704

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.0387

Gnomad FIN exome

AF:

0.0763

Gnomad NFE exome

AF:

0.0674

Gnomad OTH exome

AF:

0.0586

GnomAD4 exome

AF:

0.0608

AC:

88818

AN:

1461614

Hom.:

2944

Cov.:

AF XY:

0.0609

AC XY:

44296

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.0326

Gnomad4 ASJ exome

AF:

0.0694

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0376

Gnomad4 FIN exome

AF:

0.0775

Gnomad4 NFE exome

AF:

0.0660

Gnomad4 OTH exome

AF:

0.0561

GnomAD4 genome

AF:

0.0532

AC:

8104

AN:

152302

Hom.:

240

Cov.:

AF XY:

0.0527

AC XY:

3928

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.0522

Gnomad4 ASJ

AF:

0.0663

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.0755

Gnomad4 NFE

AF:

0.0673

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0601

Hom.:

309

Bravo

AF:

0.0504

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.0719

EpiControl

AF:

0.0653

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

EPHX1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.9

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over