1-225831898-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001136018.4(EPHX1):c.303T>C(p.Phe101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,614,210 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: EPHX1 NM_001136018.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.689

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-225831898-T-C is Benign according to our data. Variant chr1-225831898-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 721070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.689 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.303T>C	p.Phe101=	synonymous_variant	3/9	ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.303T>C	p.Phe101=	synonymous_variant	3/9	1	NM_001136018.4	P1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00150 AC: 376 AN: 251482 Hom.: 0 AF XY: 0.00161 AC XY: 219 AN XY: 135912

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.00219

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00185 AC: 2707 AN: 1461882 Hom.: 1 Cov.: 32 AF XY: 0.00186 AC XY: 1350 AN XY: 727242

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.000650

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00189

Gnomad4 FIN exome AF: 0.00198

Gnomad4 NFE exome AF: 0.00207

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00142 AC: 217 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74482

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.00130

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	3.5
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs2234699; hg19: chr1-226019599;