Variant 1-225838651-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001136018.4(EPHX1):c.365-3C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 1,613,460 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

EPHX1
NM_001136018.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.6768

Clinical Significance

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

Conservation

PhyloP100: 2.55

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=-0.38).

BP6

Variant 1-225838651-C-A is Benign according to our data. Variant chr1-225838651-C-A is described in ClinVar as [Benign]. Clinvar id is 780301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-225838651-C-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.365-3C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
EPHX1	ENST00000272167.10 linkuse as main transcript	c.365-3C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_001136018.4	ENSP00000272167	P1
EPHX1	ENST00000366837.5 linkuse as main transcript	c.365-3C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000355802	P1
EPHX1	ENST00000614058.4 linkuse as main transcript	c.365-3C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000480004	P1
EPHX1	ENST00000448202.5 linkuse as main transcript	c.365-3C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000408469

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

499

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000896

AC:

224

AN:

250100

Hom.:

AF XY:

0.000694

AC XY:

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000347

AC:

507

AN:

1461226

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

216

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.00328

AC:

500

AN:

152234

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00368

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	EPHX1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.68

dbscSNV1_RF

Benign

0.63

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