rs2740171

Variant names:

• chr1-225837827-A-C
• rs2740171
• NM_001136018.4:c.365-827A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-225837827-A-C
• chr1-225837827-A-G
• chr1-225837827-A-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.365-827A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,166 control chromosomes in the GnomAD database, including 43,472 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 0.75 (43472 hom., cov: 33)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 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.365-827A>C		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.365-827A>C		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.365-827A>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.365-827A>C		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.365-827A>C		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.365-827A>C		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114380 AN: 152048 Hom.: 43441 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.752 AC: 114462 AN: 152166 Hom.: 43472 Cov.: 33 AF XY: 0.758 AC XY: 56357 AN XY: 74398

African (AFR) AF: 0.641 AC: 26572 AN: 41478

American (AMR) AF: 0.808 AC: 12352 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2642 AN: 3468

East Asian (EAS) AF: 0.885 AC: 4589 AN: 5188

South Asian (SAS) AF: 0.847 AC: 4089 AN: 4826

European-Finnish (FIN) AF: 0.823 AC: 8712 AN: 10580

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52922 AN: 68016

Other (OTH) AF: 0.751 AC: 1585 AN: 2110

Alfa AF: 0.759 Hom.: 55265

Bravo AF: 0.748

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.43
PhyloP100		-1.9
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: rs2740171; hg19: chr1-226025528;