1-225838540-C-G

Position:

• chr1-225838540-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001136018.4(EPHX1):​c.365-114C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 827,282 control chromosomes in the GnomAD database, including 123,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20483 hom., cov: 30)
  • Exomes 𝑓: 0.55 (103198 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-225838540-C-G is Benign according to our data. Variant chr1-225838540-C-G is described in ClinVar as [Benign]. Clinvar id is 1268895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.365-114C>G		intron_variant		ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.365-114C>G		intron_variant		1	NM_001136018.4	ENSP00000272167	P1
EPHX1	ENST00000366837.5	c.365-114C>G		intron_variant		1		ENSP00000355802	P1
EPHX1	ENST00000614058.4	c.365-114C>G		intron_variant		1		ENSP00000480004	P1
EPHX1	ENST00000448202.5	c.365-114C>G		intron_variant		2		ENSP00000408469

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77266 AN: 151452 Hom.: 20481 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.549 AC: 370828 AN: 675710 Hom.: 103198 AF XY: 0.548 AC XY: 194542 AN XY: 355264

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.697

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.604

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.510 AC: 77289 AN: 151572 Hom.: 20483 Cov.: 30 AF XY: 0.518 AC XY: 38353 AN XY: 74056

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.492

Alfa AF: 0.369 Hom.: 1004

Bravo AF: 0.508

Asia WGS AF: 0.517 AC: 1801 AN: 3478

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	-0.87
CADD	Benign	0.74
DANN	Benign	0.096

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: rs4149223; hg19: chr1-226026241;