1-225831670-G-T

Position:

• chr1-225831670-G-T

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.184-109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,059,036 control chromosomes in the GnomAD database, including 32,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4799 hom., cov: 32)
  • Exomes 𝑓: 0.24 (27215 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.39

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=-0.93).
• BP6: Variant 1-225831670-G-T is Benign according to our data. Variant chr1-225831670-G-T is described in ClinVar as [Benign]. Clinvar id is 1259870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.184-109G>T		intron_variant		ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.184-109G>T		intron_variant		1	NM_001136018.4	ENSP00000272167	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38009 AN: 151962 Hom.: 4795 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.242 AC: 219242 AN: 906956 Hom.: 27215 AF XY: 0.241 AC XY: 113725 AN XY: 470964

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.250 AC: 38035 AN: 152080 Hom.: 4799 Cov.: 32 AF XY: 0.251 AC XY: 18670 AN XY: 74332

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.249

Alfa AF: 0.255 Hom.: 1555

Bravo AF: 0.246

Asia WGS AF: 0.198 AC: 692 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 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.059
DANN	Benign	0.61

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: rs3817268; hg19: chr1-226019371; COSMIC: COSV55301741;