1-225831546-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001136018.4(EPHX1):c.184-220dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.016 (28 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113

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 -10 ACMG points.

• BP6: Variant 1-225831546-C-CA is Benign according to our data. Variant chr1-225831546-C-CA is described in ClinVar as [Benign]. Clinvar id is 1272638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.184-220dup		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.184-220dup		intron_variant		1	NM_001136018.4	P1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 1718 AN: 104614 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.0140

Gnomad EAS AF: 0.00229

Gnomad SAS AF: 0.00321

Gnomad FIN AF: 0.000161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.0136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0164 AC: 1720 AN: 104644 Hom.: 28 Cov.: 0 AF XY: 0.0159 AC XY: 800 AN XY: 50234

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.00860

Gnomad4 ASJ AF: 0.0140

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.00323

Gnomad4 FIN AF: 0.000161

Gnomad4 NFE AF: 0.00218

Gnomad4 OTH AF: 0.0134

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

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs75126131; hg19: chr1-226019247;