rs10915884

Variant names:

• chr1-225836174-C-T
• rs10915884
• NM_001136018.4:c.365-2480C>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.365-2480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,196 control chromosomes in the GnomAD database, including 2,479 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 0.17 (2479 hom., cov: 32)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.365-2480C>T		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.365-2480C>T		intron_variant	Intron 3 of 8	1	NM_001136018.4	ENSP00000272167.5
EPHX1	ENST00000366837.5	c.365-2480C>T		intron_variant	Intron 3 of 8	1		ENSP00000355802.4
EPHX1	ENST00000614058.4	c.365-2480C>T		intron_variant	Intron 3 of 8	1		ENSP00000480004.1
EPHX1	ENST00000448202.5	c.365-2480C>T		intron_variant	Intron 3 of 3	2		ENSP00000408469.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25315 AN: 152078 Hom.: 2476 Cov.: 32

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.166 AC: 25323 AN: 152196 Hom.: 2479 Cov.: 32 AF XY: 0.168 AC XY: 12494 AN XY: 74404

African (AFR) AF: 0.0727 AC: 3017 AN: 41516

American (AMR) AF: 0.191 AC: 2923 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1576 AN: 5174

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4828

European-Finnish (FIN) AF: 0.164 AC: 1737 AN: 10594

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13634 AN: 68002

Other (OTH) AF: 0.154 AC: 323 AN: 2104

Alfa AF: 0.186 Hom.: 584

Bravo AF: 0.163

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		0.33
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: rs10915884; hg19: chr1-226023875; COSMIC: COSV55303925; COSMIC: COSV55303925;