1-225831560-GAAAAA-GAA

Variant names:

• chr1-225831560-GAAA-G
• rs757569759
• NM_001136018.4:c.184-215_184-213delAAA

Variant summary

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

The NM_001136018.4(EPHX1):​c.184-215_184-213delAAA 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 0.00019 (0 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• 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.184-215_184-213delAAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-215_184-213delAAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-215_184-213delAAA		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.184-218_184-216delAAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-218_184-216delAAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-218_184-216delAAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.000186 AC: 14 AN: 75430 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000546

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00284

Gnomad SAS AF: 0.000404

Gnomad FIN AF: 0.000193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000136

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000185 AC: 14 AN: 75474 Hom.: 0 Cov.: 0 AF XY: 0.000191 AC XY: 7 AN XY: 36616

African (AFR) AF: 0.0000545 AC: 1 AN: 18360

American (AMR) AF: 0.00 AC: 0 AN: 6932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1822

East Asian (EAS) AF: 0.00284 AC: 6 AN: 2112

South Asian (SAS) AF: 0.000402 AC: 1 AN: 2486

European-Finnish (FIN) AF: 0.000193 AC: 1 AN: 5172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 184

European-Non Finnish (NFE) AF: 0.000136 AC: 5 AN: 36720

Other (OTH) AF: 0.00 AC: 0 AN: 1122

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14

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: rs757569759; hg19: chr1-226019261;