rs2234697

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136018.4(EPHX1):​c.145C>A​(p.Arg49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,738 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R49C) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EPHX1
NM_001136018.4 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.763
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPHX1NM_001136018.4 linkc.145C>A p.Arg49Ser missense_variant Exon 2 of 9 ENST00000272167.10 NP_001129490.1 P07099R4SBI6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPHX1ENST00000272167.10 linkc.145C>A p.Arg49Ser missense_variant Exon 2 of 9 1 NM_001136018.4 ENSP00000272167.5 P07099

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1448738
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
719386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
.;T;.;T;T
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D;.;D;D;.
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.45
T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.3
.;M;.;M;M
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-3.6
D;D;D;.;D
REVEL
Benign
0.19
Sift
Uncertain
0.016
D;D;D;.;D
Sift4G
Uncertain
0.010
D;D;D;D;D
Polyphen
0.54
.;P;.;P;P
Vest4
0.38, 0.37, 0.38
MutPred
0.58
Gain of glycosylation at R49 (P = 0.0174);Gain of glycosylation at R49 (P = 0.0174);Gain of glycosylation at R49 (P = 0.0174);Gain of glycosylation at R49 (P = 0.0174);Gain of glycosylation at R49 (P = 0.0174);
MVP
0.48
MPC
0.32
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.51
gMVP
0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-226016575; API