rs2854461

Variant names:

• chr1-225823943-C-A
• rs2854461
• NM_001136018.4:c.-5-4782C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-225823943-C-A
• chr1-225823943-C-G
• chr1-225823943-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136018.4(EPHX1):​c.-5-4782C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,074 control chromosomes in the GnomAD database, including 7,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7915 hom., cov: 32)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.-5-4782C>A		intron_variant	Intron 1 of 8	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.-5-4782C>A		intron_variant	Intron 1 of 8	1	NM_001136018.4	ENSP00000272167.5
EPHX1	ENST00000614058.4	c.-5-4782C>A		intron_variant	Intron 1 of 8	1		ENSP00000480004.1
EPHX1	ENST00000448202.5	c.-5-4782C>A		intron_variant	Intron 1 of 3	2		ENSP00000408469.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46249 AN: 151956 Hom.: 7899 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46292 AN: 152074 Hom.: 7915 Cov.: 32 AF XY: 0.308 AC XY: 22893 AN XY: 74330

African (AFR) AF: 0.156 AC: 6475 AN: 41508

American (AMR) AF: 0.369 AC: 5635 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3466

East Asian (EAS) AF: 0.543 AC: 2796 AN: 5146

South Asian (SAS) AF: 0.479 AC: 2311 AN: 4824

European-Finnish (FIN) AF: 0.310 AC: 3283 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23404 AN: 67958

Other (OTH) AF: 0.314 AC: 661 AN: 2104

Alfa AF: 0.338 Hom.: 10891

Bravo AF: 0.302

Asia WGS AF: 0.514 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		0.20
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: rs2854461; hg19: chr1-226011644;