Genetic Variant NM_001136018.4:c.-5-3071C>T (chr1-225825654-C-T) – 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.-5-3071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,190 control chromosomes in the GnomAD database, including 4,156 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 0.21 ( 4155 hom., cov: 32)

Exomes 𝑓: 0.19 ( 1 hom. )

Consequence

EPHX1
NM_001136018.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.361

Publications

24 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4 link	c.-5-3071C>T		intron_variant	Intron 1 of 8	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EPHX1	ENST00000272167.10 link	c.-5-3071C>T	intron_variant	Intron 1 of 8	1	NM_001136018.4	ENSP00000272167.5
EPHX1	ENST00000366837.5 link	c.-6+110C>T	intron_variant	Intron 1 of 8	1		ENSP00000355802.4
EPHX1	ENST00000614058.4 link	c.-5-3071C>T	intron_variant	Intron 1 of 8	1		ENSP00000480004.1
EPHX1	ENST00000448202.5 link	c.-5-3071C>T	intron_variant	Intron 1 of 3	2		ENSP00000408469.1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32618

AN:

152046

Hom.:

4155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.192

AC:

AN:

Hom.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.214

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.214

AC:

32612

AN:

152164

Hom.:

4155

Cov.:

AF XY:

0.216

AC XY:

16078

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0809

AC:

3361

AN:

41532

American (AMR)

AF:

0.237

AC:

3618

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1026

AN:

3472

East Asian (EAS)

AF:

0.329

AC:

1693

AN:

5150

South Asian (SAS)

AF:

0.355

AC:

1711

AN:

4822

European-Finnish (FIN)

AF:

0.224

AC:

2371

AN:

10598

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18139

AN:

67978

Other (OTH)

AF:

0.207

AC:

438

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1277

2553

3830

5106

6383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.250

Hom.:

16661

Bravo

AF:

0.207

Asia WGS

AF:

0.335

AC:

1165

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.56

PhyloP100

-0.36

PromoterAI

0.0033

Neutral

(source)

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