chr1-225833287-G-A

Variant names:

• chr1-225833287-G-A
• rs2740168
• NM_001136018.4:c.364+1328G>A

Variant summary

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

The NM_001136018.4(EPHX1):​c.364+1328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,182 control chromosomes in the GnomAD database, including 15,058 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 0.43 (15058 hom., cov: 33)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 11 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.364+1328G>A		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.364+1328G>A		intron_variant	Intron 3 of 8	1	NM_001136018.4	ENSP00000272167.5
EPHX1	ENST00000366837.5	c.364+1328G>A		intron_variant	Intron 3 of 8	1		ENSP00000355802.4
EPHX1	ENST00000614058.4	c.364+1328G>A		intron_variant	Intron 3 of 8	1		ENSP00000480004.1
EPHX1	ENST00000448202.5	c.364+1328G>A		intron_variant	Intron 3 of 3	2		ENSP00000408469.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66103 AN: 152064 Hom.: 15019 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.435 AC: 66186 AN: 152182 Hom.: 15058 Cov.: 33 AF XY: 0.431 AC XY: 32046 AN XY: 74386

African (AFR) AF: 0.557 AC: 23121 AN: 41508

American (AMR) AF: 0.381 AC: 5820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2722 AN: 5186

South Asian (SAS) AF: 0.448 AC: 2157 AN: 4820

European-Finnish (FIN) AF: 0.316 AC: 3340 AN: 10578

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26612 AN: 68016

Other (OTH) AF: 0.408 AC: 861 AN: 2112

Alfa AF: 0.401 Hom.: 49321

Bravo AF: 0.441

Asia WGS AF: 0.485 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.33
PhyloP100		-0.40
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: rs2740168; hg19: chr1-226020988;