rs1051741

chr1-225844528-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001136018.4(EPHX1):c.1071C>T(p.Asn357=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,614,038 control chromosomes in the GnomAD database, including 10,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (851 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9268 hom.)
• Consequence: EPHX1 NM_001136018.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.102

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-225844528-C-T is Benign according to our data. Variant chr1-225844528-C-T is described in ClinVar as [Benign]. Clinvar id is 1179465.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-225844528-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.102 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.1071C>T	p.Asn357=	synonymous_variant	8/9	ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.1071C>T	p.Asn357=	synonymous_variant	8/9	1	NM_001136018.4	P1
EPHX1	ENST00000366837.5	c.1071C>T	p.Asn357=	synonymous_variant	8/9	1		P1
EPHX1	ENST00000614058.4	c.1071C>T	p.Asn357=	synonymous_variant	8/9	1		P1
	ENST00000424332.1	n.43+1952G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15037 AN: 152062 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.106 AC: 26723 AN: 251446 Hom.: 1878 AF XY: 0.114 AC XY: 15525 AN XY: 135898

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0439

Gnomad ASJ exome AF: 0.0678

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.0541

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.0954

GnomAD4 exome AF: 0.106 AC: 155071 AN: 1461858 Hom.: 9268 Cov.: 33 AF XY: 0.110 AC XY: 79966 AN XY: 727234

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.0737

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0989 AC: 15047 AN: 152180 Hom.: 851 Cov.: 32 AF XY: 0.0975 AC XY: 7254 AN XY: 74392

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0689

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0964 Hom.: 1517

Bravo AF: 0.0956

Asia WGS AF: 0.161 AC: 558 AN: 3478

EpiCase AF: 0.0959

EpiControl AF: 0.0960

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	14
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs1051741; hg19: chr1-226032229; COSMIC: COSV55299610; COSMIC: COSV55299610;