Variant chr1-225839958-C-T 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.852C>T(p.Pro284Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,614,140 control chromosomes in the GnomAD database, including 2,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 227 hom., cov: 32)

Exomes 𝑓: 0.047 ( 2037 hom. )

Consequence

EPHX1
NM_001136018.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0660

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:

EPHX1 (HGNC:):

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=-0.68).

BP6

Variant 1-225839958-C-T is Benign according to our data. Variant chr1-225839958-C-T is described in ClinVar as [Benign]. Clinvar id is 1295081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 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.852C>T	p.Pro284Pro	synonymous_variant	6/9	ENST00000272167.10	NP_001129490.1	P07099R4SBI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.852C>T	p.Pro284Pro	synonymous_variant	6/9	1	NM_001136018.4	ENSP00000272167.5	P07099
EPHX1	ENST00000366837.5 linkuse as main transcript	c.852C>T	p.Pro284Pro	synonymous_variant	6/9	1		ENSP00000355802.4	P07099
EPHX1	ENST00000614058.4 linkuse as main transcript	c.852C>T	p.Pro284Pro	synonymous_variant	6/9	1		ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6983

AN:

152154

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0493

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0907

Gnomad FIN

AF:

0.0814

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0399

Gnomad OTH

AF:

0.0503

GnomAD3 exomes

AF:

0.0605

AC:

15221

AN:

251488

Hom.:

571

AF XY:

0.0615

AC XY:

8363

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.0567

Gnomad ASJ exome

AF:

0.0621

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.0888

Gnomad FIN exome

AF:

0.0814

Gnomad NFE exome

AF:

0.0409

Gnomad OTH exome

AF:

0.0507

GnomAD4 exome

AF:

0.0468

AC:

68383

AN:

1461868

Hom.:

2037

Cov.:

AF XY:

0.0483

AC XY:

35092

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.0594

Gnomad4 ASJ exome

AF:

0.0595

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.0906

Gnomad4 FIN exome

AF:

0.0779

Gnomad4 NFE exome

AF:

0.0380

Gnomad4 OTH exome

AF:

0.0501

GnomAD4 genome

AF:

0.0460

AC:

7003

AN:

152272

Hom.:

227

Cov.:

AF XY:

0.0484

AC XY:

3606

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0910

Gnomad4 FIN

AF:

0.0814

Gnomad4 NFE

AF:

0.0399

Gnomad4 OTH

AF:

0.0560

Alfa

AF:

0.0410

Hom.:

283

Bravo

AF:

0.0423

Asia WGS

AF:

0.137

AC:

474

AN:

3478

EpiCase

AF:

0.0413

EpiControl

AF:

0.0403

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	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.6

DANN

Benign

0.75

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