1-225831546-CAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr1-225831546-C-CAA
• rs75126131
• NM_001136018.4:c.184-221_184-220dupAA

Variant summary

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

The NM_001136018.4(EPHX1):​c.184-221_184-220dupAA 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 0.0011 (0 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• 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.184-221_184-220dupAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-221_184-220dupAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-221_184-220dupAA		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.184-233_184-232insAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-233_184-232insAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-233_184-232insAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 114 AN: 104670 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000287

Gnomad SAS AF: 0.000583

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00109 AC: 114 AN: 104700 Hom.: 0 Cov.: 0 AF XY: 0.00115 AC XY: 58 AN XY: 50262

African (AFR) AF: 0.00278 AC: 75 AN: 27024

American (AMR) AF: 0.000101 AC: 1 AN: 9882

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

East Asian (EAS) AF: 0.000288 AC: 1 AN: 3470

South Asian (SAS) AF: 0.000587 AC: 2 AN: 3410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000706 AC: 35 AN: 49544

Other (OTH) AF: 0.00 AC: 0 AN: 1494

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

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;