Variant 1-225828680-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.-5-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,603,044 control chromosomes in the GnomAD database, including 67,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5750 hom., cov: 31)

Exomes 𝑓: 0.29 ( 61699 hom. )

Consequence

EPHX1
NM_001136018.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-225828680-G-A is Benign according to our data. Variant chr1-225828680-G-A is described in ClinVar as [Benign]. Clinvar id is 1236956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 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.-5-45G>A		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
EPHX1	ENST00000272167.10 linkuse as main transcript	c.-5-45G>A	intron_variant	1	NM_001136018.4	P1
EPHX1	ENST00000366837.5 linkuse as main transcript	c.-5-45G>A	intron_variant	1		P1
EPHX1	ENST00000614058.4 linkuse as main transcript	c.-5-45G>A	intron_variant	1		P1
EPHX1	ENST00000448202.5 linkuse as main transcript	c.-5-45G>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41385

AN:

151602

Hom.:

5752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.269

AC:

65784

AN:

244118

Hom.:

9078

AF XY:

0.270

AC XY:

35664

AN XY:

132174

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.289

AC:

419150

AN:

1451328

Hom.:

61699

Cov.:

AF XY:

0.288

AC XY:

207467

AN XY:

721290

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.273

AC:

41399

AN:

151716

Hom.:

5750

Cov.:

AF XY:

0.272

AC XY:

20130

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.216

Hom.:

753

Bravo

AF:

0.268

Asia WGS

AF:

0.191

AC:

664

AN:

3476

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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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