Variant chr1-225828932-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001136018.4(EPHX1):c.183+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 1,555,594 control chromosomes in the GnomAD database, including 8,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 691 hom., cov: 32)

Exomes 𝑓: 0.093 ( 7456 hom. )

Consequence

EPHX1
NM_001136018.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.131

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-225828932-G-A is Benign according to our data. Variant chr1-225828932-G-A is described in ClinVar as [Benign]. Clinvar id is 1266914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.183+20G>A		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.183+20G>A		intron_variant		1	NM_001136018.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12095

AN:

152112

Hom.:

681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0826

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0974

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.0967

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.0838

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.123

AC:

20007

AN:

162826

Hom.:

1550

AF XY:

0.124

AC XY:

10688

AN XY:

86250

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.0987

Gnomad NFE exome

AF:

0.0849

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0933

AC:

130901

AN:

1403364

Hom.:

7456

Cov.:

AF XY:

0.0960

AC XY:

66496

AN XY:

692882

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.0913

Gnomad4 NFE exome

AF:

0.0816

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0796

AC:

12124

AN:

152230

Hom.:

691

Cov.:

AF XY:

0.0833

AC XY:

6197

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.0974

Gnomad4 EAS

AF:

0.230

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.0967

Gnomad4 NFE

AF:

0.0839

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0810

Hom.:

104

Bravo

AF:

0.0808

Asia WGS

AF:

0.188

AC:

653

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

DANN

Benign

0.81

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

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