1-225828680-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.-5-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,603,044 control chromosomes in the GnomAD database, including 67,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5750 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61699 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.47

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=-0.93).
• BP6: Variant 1-225828680-G-A is Benign according to our data. Variant chr1-225828680-G-A is described in ClinVar as [Benign]. Clinvar id is 1236956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) 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.-5-45G>A		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.-5-45G>A		intron_variant		1	NM_001136018.4	P1
EPHX1	ENST00000366837.5	c.-5-45G>A		intron_variant		1		P1
EPHX1	ENST00000614058.4	c.-5-45G>A		intron_variant		1		P1
EPHX1	ENST00000448202.5	c.-5-45G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41385 AN: 151602 Hom.: 5752 Cov.: 31

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.283

GnomAD3 exomes AF: 0.269 AC: 65784 AN: 244118 Hom.: 9078 AF XY: 0.270 AC XY: 35664 AN XY: 132174

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.289 AC: 419150 AN: 1451328 Hom.: 61699 Cov.: 29 AF XY: 0.288 AC XY: 207467 AN XY: 721290

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.273 AC: 41399 AN: 151716 Hom.: 5750 Cov.: 31 AF XY: 0.272 AC XY: 20130 AN XY: 74100

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.280

Alfa AF: 0.216 Hom.: 753

Bravo AF: 0.268

Asia WGS AF: 0.191 AC: 664 AN: 3476

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	-0.93
Cadd	Benign	0.13
Dann	Benign	0.63
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

Other links and lift over

dbSNP: rs41266229; hg19: chr1-226016381; COSMIC: COSV55300387; COSMIC: COSV55300387;