1-225828932-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001136018.4(EPHX1):c.183+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 1,555,594 control chromosomes in the GnomAD database, including 8,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (691 hom., cov: 32)
  • Exomes 𝑓: 0.093 (7456 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.131

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-225828932-G-A is Benign according to our data. Variant chr1-225828932-G-A is described in ClinVar as [Benign]. Clinvar id is 1266914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.183+20G>A		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.183+20G>A		intron_variant		1	NM_001136018.4	P1

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12095 AN: 152112 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.123 AC: 20007 AN: 162826 Hom.: 1550 AF XY: 0.124 AC XY: 10688 AN XY: 86250

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.239

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.0987

Gnomad NFE exome AF: 0.0849

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0933 AC: 130901 AN: 1403364 Hom.: 7456 Cov.: 33 AF XY: 0.0960 AC XY: 66496 AN XY: 692882

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.0913

Gnomad4 NFE exome AF: 0.0816

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0796 AC: 12124 AN: 152230 Hom.: 691 Cov.: 32 AF XY: 0.0833 AC XY: 6197 AN XY: 74412

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0810 Hom.: 104

Bravo AF: 0.0808

Asia WGS AF: 0.188 AC: 653 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.8
Dann	Benign	0.81

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: rs3738047; hg19: chr1-226016633; COSMIC: COSV55301343;