Genetic Variant NM_001136018.4:c.364+1328G>A (chr1-225833287-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001136018.4(EPHX1):c.364+1328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,182 control chromosomes in the GnomAD database, including 15,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15058 hom., cov: 33)

Consequence

EPHX1
NM_001136018.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

Publications

11 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: AD 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4 link	c.364+1328G>A		intron_variant	Intron 3 of 8	ENST00000272167.10	NP_001129490.1	P07099R4SBI6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPHX1	ENST00000272167.10 link	c.364+1328G>A	intron_variant	Intron 3 of 8	1	NM_001136018.4	ENSP00000272167.5	P07099
EPHX1	ENST00000366837.5 link	c.364+1328G>A	intron_variant	Intron 3 of 8	1		ENSP00000355802.4	P07099
EPHX1	ENST00000614058.4 link	c.364+1328G>A	intron_variant	Intron 3 of 8	1		ENSP00000480004.1	P07099
EPHX1	ENST00000448202.5 link	c.364+1328G>A	intron_variant	Intron 3 of 3	2		ENSP00000408469.1	B1AQP8

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66103

AN:

152064

Hom.:

15019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.408

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

GnomAD4 genome

AF:

0.435

AC:

66186

AN:

152182

Hom.:

15058

Cov.:

AF XY:

0.431

AC XY:

32046

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.557

AC:

23121

AN:

41508

American (AMR)

AF:

0.381

AC:

5820

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3470

East Asian (EAS)

AF:

0.525

AC:

2722

AN:

5186

South Asian (SAS)

AF:

0.448

AC:

2157

AN:

4820

European-Finnish (FIN)

AF:

0.316

AC:

3340

AN:

10578

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.391

AC:

26612

AN:

68016

Other (OTH)

AF:

0.408

AC:

861

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1890

3781

5671

7562

9452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.401

Hom.:

49321

Bravo

AF:

0.441

Asia WGS

AF:

0.485

AC:

1686

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.25

(source)

DANN

Benign

0.33

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over