rs1131873

chr1-225831952-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Benign. Variant got -13 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_single_submitter, 1 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	UniProt
EPHX1	NM_001136018.4	c.357G>A	p.Lys119=	synonymous_variant	3/9	ENST00000272167.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21791 AN: 152054 Hom.: 1704 Cov.: 33

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

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.: 36 AF XY: 0.153 AC XY: 111289 AN XY: 727086

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.: 33 AF XY: 0.144 AC XY: 10703 AN XY: 74364

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:1

Revision: criteria provided, single submitter

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	-0.26
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

Other links and lift over

dbSNP: rs1131873; hg19: chr1-226019653; COSMIC: COSV55300861;