1-225827261-C-T

Variant names:

• chr1-225827261-C-T
• rs2854455
• NM_001136018.4:c.-5-1464C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136018.4(EPHX1):​c.-5-1464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,952 control chromosomes in the GnomAD database, including 39,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (39403 hom., cov: 31)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 5 publications found

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]

EPHX1 Gene-Disease associations (from GenCC):

• familial hypercholanemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136018.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	NM_001136018.4	MANE Select	c.-5-1464C>T		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.-5-1464C>T		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.-5-1464C>T		intron	N/A	NP_001278092.1	P07099

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	ENST00000272167.10	TSL:1 MANE Select	c.-5-1464C>T		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.-5-1464C>T		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.-5-1464C>T		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106536 AN: 151834 Hom.: 39389 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.701 AC: 106584 AN: 151952 Hom.: 39403 Cov.: 31 AF XY: 0.709 AC XY: 52639 AN XY: 74274

African (AFR) AF: 0.448 AC: 18533 AN: 41386

American (AMR) AF: 0.767 AC: 11703 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2616 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4642 AN: 5162

South Asian (SAS) AF: 0.926 AC: 4457 AN: 4812

European-Finnish (FIN) AF: 0.801 AC: 8473 AN: 10582

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.789 AC: 53612 AN: 67966

Other (OTH) AF: 0.721 AC: 1524 AN: 2114

Alfa AF: 0.741 Hom.: 5099

Bravo AF: 0.685

Asia WGS AF: 0.893 AC: 3103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2854455; hg19: chr1-226014962;