rs3738047

Variant names:

• chr1-225828932-G-A
• rs3738047
• NM_001136018.4:c.183+20G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-225828932-G-A
• chr1-225828932-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136018.4(EPHX1):​c.183+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 1,555,594 control chromosomes in the GnomAD database, including 8,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (691 hom., cov: 32)
  • Exomes 𝑓: 0.093 (7456 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.131
• Publications: 12 publications found

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]

EPHX1 Gene-Disease associations (from GenCC):

• familial hypercholanemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-225828932-G-A is Benign according to our data. Variant chr1-225828932-G-A is described in ClinVar as Benign. ClinVar VariationId is 1266914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.183+20G>A		intron_variant	Intron 2 of 8	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.183+20G>A		intron_variant	Intron 2 of 8	1	NM_001136018.4	ENSP00000272167.5

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12095 AN: 152112 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.123 AC: 20007 AN: 162826 AF XY: 0.124

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.239

Gnomad FIN exome AF: 0.0987

Gnomad NFE exome AF: 0.0849

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0933 AC: 130901 AN: 1403364 Hom.: 7456 Cov.: 33 AF XY: 0.0960 AC XY: 66496 AN XY: 692882

African (AFR) AF: 0.0146 AC: 466 AN: 31828

American (AMR) AF: 0.178 AC: 6427 AN: 36146

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2559 AN: 25364

East Asian (EAS) AF: 0.249 AC: 9016 AN: 36230

South Asian (SAS) AF: 0.161 AC: 12989 AN: 80428

European-Finnish (FIN) AF: 0.0913 AC: 4524 AN: 49552

Middle Eastern (MID) AF: 0.149 AC: 745 AN: 5004

European-Non Finnish (NFE) AF: 0.0816 AC: 88213 AN: 1080672

Other (OTH) AF: 0.103 AC: 5962 AN: 58140

GnomAD4 genome AF: 0.0796 AC: 12124 AN: 152230 Hom.: 691 Cov.: 32 AF XY: 0.0833 AC XY: 6197 AN XY: 74412

African (AFR) AF: 0.0171 AC: 710 AN: 41564

American (AMR) AF: 0.130 AC: 1993 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1189 AN: 5170

South Asian (SAS) AF: 0.169 AC: 810 AN: 4806

European-Finnish (FIN) AF: 0.0967 AC: 1025 AN: 10600

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5703 AN: 68012

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.0810 Hom.: 104

Bravo AF: 0.0808

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.81
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3738047; hg19: chr1-226016633; COSMIC: COSV55301343;