1-225831560-GAAAAA-GAAA

Variant names:

• chr1-225831560-GAA-G
• rs757569759
• NM_001136018.4:c.184-214_184-213delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001136018.4(EPHX1):​c.184-214_184-213delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (476 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-225831560-GAA-G is Benign according to our data. Variant chr1-225831560-GAA-G is described in ClinVar as Benign. ClinVar VariationId is 1234932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 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.184-214_184-213delAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-214_184-213delAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-214_184-213delAA		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_184-217delAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-218_184-217delAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-218_184-217delAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.141 AC: 10672 AN: 75422 Hom.: 476 Cov.: 0

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0800

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.141 AC: 10671 AN: 75466 Hom.: 476 Cov.: 0 AF XY: 0.145 AC XY: 5314 AN XY: 36608

African (AFR) AF: 0.0410 AC: 753 AN: 18360

American (AMR) AF: 0.164 AC: 1140 AN: 6932

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 270 AN: 1822

East Asian (EAS) AF: 0.310 AC: 655 AN: 2112

South Asian (SAS) AF: 0.273 AC: 678 AN: 2484

European-Finnish (FIN) AF: 0.155 AC: 800 AN: 5168

Middle Eastern (MID) AF: 0.0761 AC: 14 AN: 184

European-Non Finnish (NFE) AF: 0.164 AC: 6037 AN: 36718

Other (OTH) AF: 0.150 AC: 168 AN: 1122

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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;