1-225827415-A-G

Variant names:

• chr1-225827415-A-G
• rs2671272
• NM_001136018.4:c.-5-1310A>G

Variant summary

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

The NM_001136018.4(EPHX1):​c.-5-1310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,132 control chromosomes in the GnomAD database, including 39,280 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 0.70 (39280 hom., cov: 32)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 15 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 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.-5-1310A>G		intron	N/A	NP_001129490.1
	EPHX1	NM_000120.4		c.-5-1310A>G		intron	N/A	NP_000111.1
	EPHX1	NM_001291163.2		c.-5-1310A>G		intron	N/A	NP_001278092.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	ENST00000272167.10	TSL:1 MANE Select	c.-5-1310A>G		intron	N/A	ENSP00000272167.5
	EPHX1	ENST00000366837.5	TSL:1	c.-5-1310A>G		intron	N/A	ENSP00000355802.4
	EPHX1	ENST00000614058.4	TSL:1	c.-5-1310A>G		intron	N/A	ENSP00000480004.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106310 AN: 152014 Hom.: 39258 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.699 AC: 106365 AN: 152132 Hom.: 39280 Cov.: 32 AF XY: 0.706 AC XY: 52529 AN XY: 74382

African (AFR) AF: 0.440 AC: 18245 AN: 41464

American (AMR) AF: 0.766 AC: 11707 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2617 AN: 3468

East Asian (EAS) AF: 0.900 AC: 4664 AN: 5182

South Asian (SAS) AF: 0.926 AC: 4475 AN: 4832

European-Finnish (FIN) AF: 0.801 AC: 8485 AN: 10594

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53617 AN: 67990

Other (OTH) AF: 0.724 AC: 1531 AN: 2114

Alfa AF: 0.763 Hom.: 193914

Bravo AF: 0.683

Asia WGS AF: 0.895 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-0.85
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: rs2671272; hg19: chr1-226015116;