1-225832073-G-C

Position:

• chr1-225832073-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136018.4(EPHX1):​c.364+114G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,097,962 control chromosomes in the GnomAD database, including 284,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35973 hom., cov: 33)
  • Exomes 𝑓: 0.72 (248152 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.234

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 1-225832073-G-C is Benign according to our data. Variant chr1-225832073-G-C is described in ClinVar as [Benign]. Clinvar id is 1234219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.364+114G>C		intron_variant		ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.364+114G>C		intron_variant		1	NM_001136018.4	ENSP00000272167	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103553 AN: 151990 Hom.: 35923 Cov.: 33

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.685

GnomAD4 exome AF: 0.720 AC: 681283 AN: 945854 Hom.: 248152 Cov.: 12 AF XY: 0.725 AC XY: 353026 AN XY: 487158

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.755

Gnomad4 EAS exome AF: 0.954

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.681 AC: 103656 AN: 152108 Hom.: 35973 Cov.: 33 AF XY: 0.687 AC XY: 51072 AN XY: 74352

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.686

Alfa AF: 0.680 Hom.: 4244

Bravo AF: 0.681

Asia WGS AF: 0.880 AC: 3059 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.9
DANN	Benign	0.30

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: rs2260863; hg19: chr1-226019774; COSMIC: COSV55303895;