NM_001136018.4:c.364+1328G>A

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

2

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

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
EPHX1NM_001136018.4 linkc.364+1328G>A intron_variant Intron 3 of 8 ENST00000272167.10 NP_001129490.1 P07099R4SBI6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPHX1ENST00000272167.10 linkc.364+1328G>A intron_variant Intron 3 of 8 1 NM_001136018.4 ENSP00000272167.5 P07099
EPHX1ENST00000366837.5 linkc.364+1328G>A intron_variant Intron 3 of 8 1 ENSP00000355802.4 P07099
EPHX1ENST00000614058.4 linkc.364+1328G>A intron_variant Intron 3 of 8 1 ENSP00000480004.1 P07099
EPHX1ENST00000448202.5 linkc.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.:
33
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.:
33
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
0
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
0
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
DANN
Benign
0.33
PhyloP100
-0.40
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

Publications

Other links and lift over

dbSNP: rs2740168; hg19: chr1-226020988; API