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rs4149229

chr1-225845227-G-Achr1-225845227-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001136018.4(EPHX1):c.1248G>A(p.Lys416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,614,102 control chromosomes in the GnomAD database, including 473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 144 hom., cov: 32)
Exomes 𝑓: 0.0057 ( 329 hom. )

Consequence

EPHX1
NM_001136018.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-225845227-G-A is Benign according to our data. Variant chr1-225845227-G-A is described in ClinVar as [Benign]. Clinvar id is 1223052.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.44 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPHX1NM_001136018.4 linkuse as main transcriptc.1248G>A p.Lys416= synonymous_variant 9/9 ENST00000272167.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPHX1ENST00000272167.10 linkuse as main transcriptc.1248G>A p.Lys416= synonymous_variant 9/91 NM_001136018.4 P1
EPHX1ENST00000366837.5 linkuse as main transcriptc.1248G>A p.Lys416= synonymous_variant 9/91 P1
EPHX1ENST00000614058.4 linkuse as main transcriptc.1248G>A p.Lys416= synonymous_variant 9/91 P1
ENST00000424332.1 linkuse as main transcriptn.43+1253C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0261
AC:
3973
AN:
152172
Hom.:
142
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0786
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00844
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.0878
Gnomad SAS
AF:
0.0103
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.0196
GnomAD3 exomes
AF:
0.0131
AC:
3294
AN:
251448
Hom.:
132
AF XY:
0.0111
AC XY:
1512
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.0795
Gnomad AMR exome
AF:
0.00327
Gnomad ASJ exome
AF:
0.00109
Gnomad EAS exome
AF:
0.0849
Gnomad SAS exome
AF:
0.00608
Gnomad FIN exome
AF:
0.000508
Gnomad NFE exome
AF:
0.000624
Gnomad OTH exome
AF:
0.00798
GnomAD4 exome
AF:
0.00565
AC:
8263
AN:
1461812
Hom.:
329
Cov.:
33
AF XY:
0.00542
AC XY:
3940
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0811
Gnomad4 AMR exome
AF:
0.00396
Gnomad4 ASJ exome
AF:
0.00103
Gnomad4 EAS exome
AF:
0.0905
Gnomad4 SAS exome
AF:
0.00653
Gnomad4 FIN exome
AF:
0.000262
Gnomad4 NFE exome
AF:
0.000396
Gnomad4 OTH exome
AF:
0.0114
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0262
AC:
3992
AN:
152290
Hom.:
144
Cov.:
32
AF XY:
0.0256
AC XY:
1904
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0788
Gnomad4 AMR
AF:
0.00843
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.0882
Gnomad4 SAS
AF:
0.00994
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.0208
Alfa
AF:
0.00665
Hom.:
75
Bravo
AF:
0.0293
Asia WGS
AF:
0.0660
AC:
230
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000711

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
6.3
Dann
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4149229; hg19: chr1-226032928; COSMIC: COSV55302962; COSMIC: COSV55302962; API