Variant chr1-225831952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001136018.4(EPHX1):c.357G>A(p.Lys119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,702 control chromosomes in the GnomAD database, including 19,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1712 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17792 hom. )

Consequence

EPHX1
NM_001136018.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.38

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 1-225831952-G-A is Benign according to our data. Variant chr1-225831952-G-A is described in ClinVar as [Benign]. Clinvar id is 1286409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 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.357G>A	p.Lys119=	synonymous_variant	3/9	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10 linkuse as main transcript	c.357G>A	p.Lys119=	synonymous_variant	3/9	1	NM_001136018.4	ENSP00000272167	P1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21791

AN:

152054

Hom.:

1704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.158

AC:

39728

AN:

251312

Hom.:

3593

AF XY:

0.162

AC XY:

22019

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.151

AC:

220586

AN:

1461530

Hom.:

17792

Cov.:

AF XY:

0.153

AC XY:

111289

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.311

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.143

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.143

AC:

21804

AN:

152172

Hom.:

1712

Cov.:

AF XY:

0.144

AC XY:

10703

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.144

Hom.:

2991

Bravo

AF:

0.143

Asia WGS

AF:

0.267

AC:

926

AN:

3478

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

-0.26

CADD

Benign

6.1

DANN

Benign

0.67

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