NM_001136018.4:c.184-226_184-220delAAAAAAA

Variant names:

• chr1-225831546-CAAAAAAA-C
• rs75126131
• NM_001136018.4:c.184-226_184-220delAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001136018.4(EPHX1):​c.184-226_184-220delAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000076 (0 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.184-226_184-220delAAAAAAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-226_184-220delAAAAAAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-226_184-220delAAAAAAA		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.184-232_184-226delAAAAAAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-232_184-226delAAAAAAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-232_184-226delAAAAAAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.0000764 AC: 8 AN: 104672 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000483

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000404

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000764 AC: 8 AN: 104672 Hom.: 0 Cov.: 0 AF XY: 0.000119 AC XY: 6 AN XY: 50226

African (AFR) AF: 0.000111 AC: 3 AN: 26956

American (AMR) AF: 0.00 AC: 0 AN: 9876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2718

East Asian (EAS) AF: 0.00 AC: 0 AN: 3488

South Asian (SAS) AF: 0.00 AC: 0 AN: 3428

European-Finnish (FIN) AF: 0.000483 AC: 3 AN: 6212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.0000404 AC: 2 AN: 49554

Other (OTH) AF: 0.00 AC: 0 AN: 1476

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75126131; hg19: chr1-226019247;