1-225837096-T-C

Variant names:

• chr1-225837096-T-C
• rs2740170
• NM_001136018.4:c.365-1558T>C

Variant summary

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

The NM_001136018.4(EPHX1):​c.365-1558T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 151,320 control chromosomes in the GnomAD database, including 48,142 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 0.80 (48142 hom., cov: 32)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 18 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.365-1558T>C		intron_variant	Intron 3 of 8	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.365-1558T>C		intron_variant	Intron 3 of 8	1	NM_001136018.4	ENSP00000272167.5
EPHX1	ENST00000366837.5	c.365-1558T>C		intron_variant	Intron 3 of 8	1		ENSP00000355802.4
EPHX1	ENST00000614058.4	c.365-1558T>C		intron_variant	Intron 3 of 8	1		ENSP00000480004.1
EPHX1	ENST00000448202.5	c.365-1558T>C		intron_variant	Intron 3 of 3	2		ENSP00000408469.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 120802 AN: 151198 Hom.: 48095 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.799 AC: 120909 AN: 151320 Hom.: 48142 Cov.: 32 AF XY: 0.803 AC XY: 59415 AN XY: 73952

African (AFR) AF: 0.791 AC: 32166 AN: 40666

American (AMR) AF: 0.826 AC: 12606 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2644 AN: 3470

East Asian (EAS) AF: 0.961 AC: 4993 AN: 5194

South Asian (SAS) AF: 0.865 AC: 4174 AN: 4828

European-Finnish (FIN) AF: 0.823 AC: 8707 AN: 10578

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52965 AN: 68016

Other (OTH) AF: 0.784 AC: 1647 AN: 2102

Alfa AF: 0.783 Hom.: 89573

Bravo AF: 0.794

Asia WGS AF: 0.905 AC: 3145 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		-0.45
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: rs2740170; hg19: chr1-226024797;