1-225831560-GAAAAA-GA

Variant names:

• chr1-225831560-GAAAA-G
• rs757569759
• NM_001136018.4:c.184-216_184-213delAAAA

Variant summary

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

The NM_001136018.4(EPHX1):​c.184-216_184-213delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.061 (101 hom., cov: 0)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140
• 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-GAAAA-G is Benign according to our data. Variant chr1-225831560-GAAAA-G is described in ClinVar as Benign. ClinVar VariationId is 1289817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0864 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.184-216_184-213delAAAA		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.184-216_184-213delAAAA		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.184-216_184-213delAAAA		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_184-215delAAAA		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.184-218_184-215delAAAA		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.184-218_184-215delAAAA		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 4573 AN: 75412 Hom.: 101 Cov.: 0

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00142

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0100

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0606 AC: 4571 AN: 75456 Hom.: 101 Cov.: 0 AF XY: 0.0586 AC XY: 2147 AN XY: 36612

African (AFR) AF: 0.0192 AC: 353 AN: 18358

American (AMR) AF: 0.0512 AC: 355 AN: 6932

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 32 AN: 1822

East Asian (EAS) AF: 0.00142 AC: 3 AN: 2112

South Asian (SAS) AF: 0.0261 AC: 65 AN: 2486

European-Finnish (FIN) AF: 0.0745 AC: 385 AN: 5168

Middle Eastern (MID) AF: 0.0109 AC: 2 AN: 184

European-Non Finnish (NFE) AF: 0.0889 AC: 3264 AN: 36708

Other (OTH) AF: 0.0481 AC: 54 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		0.014
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: rs757569759; hg19: chr1-226019261;