1-225831546-CAAAAAAAA-CAAA

Variant names:

• chr1-225831546-CAAAAA-C
• rs75126131
• NM_001136018.4:c.184-224_184-220delAAAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001136018.4(EPHX1):​c.184-224_184-220delAAAAA 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 0.016 (44 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 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.184-224_184-220delAAAAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-224_184-220delAAAAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-224_184-220delAAAAA		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_184-228delAAAAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-232_184-228delAAAAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-232_184-228delAAAAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 1681 AN: 104670 Hom.: 44 Cov.: 0

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.000875

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0155

Gnomad NFE AF: 0.000626

Gnomad OTH AF: 0.0136

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

GnomAD4 genome AF: 0.0161 AC: 1689 AN: 104700 Hom.: 44 Cov.: 0 AF XY: 0.0163 AC XY: 819 AN XY: 50260

African (AFR) AF: 0.0532 AC: 1437 AN: 27022

American (AMR) AF: 0.0124 AC: 123 AN: 9882

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

East Asian (EAS) AF: 0.0205 AC: 71 AN: 3470

South Asian (SAS) AF: 0.000880 AC: 3 AN: 3410

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

Middle Eastern (MID) AF: 0.0167 AC: 4 AN: 240

European-Non Finnish (NFE) AF: 0.000626 AC: 31 AN: 49546

Other (OTH) AF: 0.0134 AC: 20 AN: 1494

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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;