rs2260863

Variant names:

• chr1-225832073-G-C
• rs2260863
• NM_001136018.4:c.364+114G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-225832073-G-C
• chr1-225832073-G-A

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.364+114G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,097,962 control chromosomes in the GnomAD database, including 284,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35973 hom., cov: 33)
  • Exomes 𝑓: 0.72 (248152 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.234
• Publications: 22 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: Unknown 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=-1.01).
• BP6: Variant 1-225832073-G-C is Benign according to our data. Variant chr1-225832073-G-C is described in ClinVar as Benign. ClinVar VariationId is 1234219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136018.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	NM_001136018.4	MANE Select	c.364+114G>C		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.364+114G>C		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.364+114G>C		intron	N/A	NP_001278092.1	P07099

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	ENST00000272167.10	TSL:1 MANE Select	c.364+114G>C		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.364+114G>C		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.364+114G>C		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103553 AN: 151990 Hom.: 35923 Cov.: 33

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.685

GnomAD4 exome AF: 0.720 AC: 681283 AN: 945854 Hom.: 248152 Cov.: 12 AF XY: 0.725 AC XY: 353026 AN XY: 487158

African (AFR) AF: 0.558 AC: 13332 AN: 23912

American (AMR) AF: 0.801 AC: 29744 AN: 37128

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 16945 AN: 22456

East Asian (EAS) AF: 0.954 AC: 34432 AN: 36086

South Asian (SAS) AF: 0.831 AC: 59525 AN: 71598

European-Finnish (FIN) AF: 0.692 AC: 27095 AN: 39160

Middle Eastern (MID) AF: 0.691 AC: 3206 AN: 4638

European-Non Finnish (NFE) AF: 0.698 AC: 465810 AN: 667350

Other (OTH) AF: 0.717 AC: 31194 AN: 43526

GnomAD4 genome AF: 0.681 AC: 103656 AN: 152108 Hom.: 35973 Cov.: 33 AF XY: 0.687 AC XY: 51072 AN XY: 74352

African (AFR) AF: 0.560 AC: 23245 AN: 41486

American (AMR) AF: 0.747 AC: 11406 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2641 AN: 3468

East Asian (EAS) AF: 0.954 AC: 4944 AN: 5184

South Asian (SAS) AF: 0.844 AC: 4071 AN: 4826

European-Finnish (FIN) AF: 0.702 AC: 7420 AN: 10566

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47623 AN: 67988

Other (OTH) AF: 0.686 AC: 1450 AN: 2114

Alfa AF: 0.680 Hom.: 4244

Bravo AF: 0.681

Asia WGS AF: 0.880 AC: 3059 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.9
DANN	Benign	0.30
PhyloP100		0.23
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: rs2260863; hg19: chr1-226019774; COSMIC: COSV55303895;