1-225827658-C-T

Variant names:

• chr1-225827658-C-T
• rs2854456
• NM_001136018.4:c.-5-1067C>T

Variant summary

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

The NM_000120.4(EPHX1):​c.-5-1067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,076 control chromosomes in the GnomAD database, including 4,134 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 0.21 (4134 hom., cov: 33)
• Consequence: EPHX1 NM_000120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000120.4. 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.-5-1067C>T		intron	N/A	NP_001129490.1
	EPHX1	NM_000120.4		c.-5-1067C>T		intron	N/A	NP_000111.1
	EPHX1	NM_001291163.2		c.-5-1067C>T		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.-5-1067C>T		intron	N/A	ENSP00000272167.5
	EPHX1	ENST00000366837.5	TSL:1	c.-5-1067C>T		intron	N/A	ENSP00000355802.4
	EPHX1	ENST00000614058.4	TSL:1	c.-5-1067C>T		intron	N/A	ENSP00000480004.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32428 AN: 151958 Hom.: 4135 Cov.: 33

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.213 AC: 32420 AN: 152076 Hom.: 4134 Cov.: 33 AF XY: 0.215 AC XY: 15977 AN XY: 74348

African (AFR) AF: 0.0762 AC: 3164 AN: 41508

American (AMR) AF: 0.236 AC: 3596 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1717 AN: 5162

South Asian (SAS) AF: 0.356 AC: 1717 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2359 AN: 10572

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18159 AN: 67970

Other (OTH) AF: 0.205 AC: 432 AN: 2106

Alfa AF: 0.250 Hom.: 9445

Bravo AF: 0.206

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.61
PhyloP100		-1.2
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: rs2854456; hg19: chr1-226015359;