1-225831546-CAAAAAAAA-CAAAAAA

Variant names:

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

Variant summary

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

The NM_001136018.4(EPHX1):​c.184-221_184-220delAA 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 0.00050 (0 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: 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_184-220delAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-221_184-220delAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-221_184-220delAA		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_184-231delAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-232_184-231delAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-232_184-231delAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.000459 AC: 48 AN: 104628 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00717

Gnomad SAS AF: 0.000292

Gnomad FIN AF: 0.00161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000141

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000497 AC: 52 AN: 104658 Hom.: 0 Cov.: 0 AF XY: 0.000557 AC XY: 28 AN XY: 50236

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000370 AC: 10 AN: 27018

American (AMR) AF: 0.00 AC: 0 AN: 9878

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

East Asian (EAS) AF: 0.00692 AC: 24 AN: 3470

South Asian (SAS) AF: 0.000293 AC: 1 AN: 3410

European-Finnish (FIN) AF: 0.00161 AC: 10 AN: 6196

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

European-Non Finnish (NFE) AF: 0.000141 AC: 7 AN: 49532

Other (OTH) AF: 0.00 AC: 0 AN: 1490

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000780064), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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

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: rs75126131; hg19: chr1-226019247;