Genetic Variant EPHX1:c.184-219_184-214delGAAAAA (chr1-225831554-AAAAAAG-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001136018.4(EPHX1):c.184-219_184-214delGAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 1572 hom., cov: 0)

Consequence

EPHX1
NM_001136018.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Publications

0 publications found

Variant links:

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

EPHX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-225831554-AAAAAAG-A is Benign according to our data. Variant chr1-225831554-AAAAAAG-A is described in ClinVar as Benign. ClinVar VariationId is 1269503.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPHX1	NM_001136018.4	MANE Select	c.184-219_184-214delGAAAAA	intron	N/A	NP_001129490.1	R4SBI6
EPHX1	NM_000120.4		c.184-219_184-214delGAAAAA	intron	N/A	NP_000111.1	R4SBI6
EPHX1	NM_001291163.2		c.184-219_184-214delGAAAAA	intron	N/A	NP_001278092.1	P07099

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPHX1	ENST00000272167.10	TSL:1 MANE Select	c.184-224_184-219delAAAAAG	intron	N/A	ENSP00000272167.5	P07099
EPHX1	ENST00000366837.5	TSL:1	c.184-224_184-219delAAAAAG	intron	N/A	ENSP00000355802.4	P07099
EPHX1	ENST00000614058.4	TSL:1	c.184-224_184-219delAAAAAG	intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

20108

AN:

120860

Hom.:

1572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0728

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.0863

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.156

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

GnomAD4 genome

AF:

0.166

AC:

20106

AN:

120934

Hom.:

1572

Cov.:

AF XY:

0.171

AC XY:

10012

AN XY:

58660

show subpopulations

African (AFR)

AF:

0.0727

AC:

2389

AN:

32850

American (AMR)

AF:

0.238

AC:

2920

AN:

12282

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

577

AN:

2872

East Asian (EAS)

AF:

0.300

AC:

1158

AN:

3860

South Asian (SAS)

AF:

0.310

AC:

1117

AN:

3608

European-Finnish (FIN)

AF:

0.169

AC:

1370

AN:

8118

Middle Eastern (MID)

AF:

0.0871

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.187

AC:

10235

AN:

54852

Other (OTH)

AF:

0.155

AC:

254

AN:

1644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

731

1462

2194

2925

3656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.126

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over