Variant 1-225831799-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001136018.4(EPHX1):c.204T>C(p.Asp68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,094 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.019 ( 303 hom. )

Consequence

EPHX1
NM_001136018.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.19

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-225831799-T-C is Benign according to our data. Variant chr1-225831799-T-C is described in ClinVar as [Benign]. Clinvar id is 3037613.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1819/152266) while in subpopulation NFE AF= 0.0199 (1355/68022). AF 95% confidence interval is 0.019. There are 18 homozygotes in gnomad4. There are 791 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.204T>C	p.Asp68=	synonymous_variant	3/9	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.204T>C	p.Asp68=	synonymous_variant	3/9	1	NM_001136018.4	ENSP00000272167	P1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1818

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00369

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00725

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0116

AC:

2911

AN:

251488

Hom.:

AF XY:

0.0117

AC XY:

1589

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00558

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00363

Gnomad FIN exome

AF:

0.00725

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0187

AC:

27329

AN:

1461828

Hom.:

303

Cov.:

AF XY:

0.0181

AC XY:

13175

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.00595

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.00758

Gnomad4 NFE exome

AF:

0.0228

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0119

AC:

1819

AN:

152266

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

791

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00368

Gnomad4 AMR

AF:

0.00922

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00725

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.0180

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0183

EpiControl

AF:

0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EPHX1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2019

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

-0.83

CADD

Benign

1.3

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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