Variant 1-225828696-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.-5-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,605,740 control chromosomes in the GnomAD database, including 68,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6304 hom., cov: 30)

Exomes 𝑓: 0.29 ( 62640 hom. )

Consequence

EPHX1
NM_001136018.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.273

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=-0.88).

BP6

Variant 1-225828696-G-A is Benign according to our data. Variant chr1-225828696-G-A is described in ClinVar as [Benign]. Clinvar id is 1269020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4 linkuse as main transcript	c.-5-29G>A		intron_variant		ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
EPHX1	ENST00000272167.10 linkuse as main transcript	c.-5-29G>A	intron_variant	1	NM_001136018.4	ENSP00000272167	P1
EPHX1	ENST00000366837.5 linkuse as main transcript	c.-5-29G>A	intron_variant	1		ENSP00000355802	P1
EPHX1	ENST00000614058.4 linkuse as main transcript	c.-5-29G>A	intron_variant	1		ENSP00000480004	P1
EPHX1	ENST00000448202.5 linkuse as main transcript	c.-5-29G>A	intron_variant	2		ENSP00000408469

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

43467

AN:

150070

Hom.:

6307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.343

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.272

AC:

67704

AN:

248996

Hom.:

9511

AF XY:

0.271

AC XY:

36558

AN XY:

134716

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.291

AC:

423376

AN:

1455560

Hom.:

62640

Cov.:

AF XY:

0.289

AC XY:

209496

AN XY:

723724

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.240

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.290

AC:

43485

AN:

150180

Hom.:

6304

Cov.:

AF XY:

0.288

AC XY:

21093

AN XY:

73332

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.296

Hom.:

2628

Bravo

AF:

0.285

Asia WGS

AF:

0.193

AC:

671

AN:

3476

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.88

CADD

Benign

3.0

DANN

Benign

0.50

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