chr1-225825654-C-T

Variant names:

• chr1-225825654-C-T
• rs1877724
• NM_001136018.4:c.-5-3071C>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.-5-3071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,190 control chromosomes in the GnomAD database, including 4,156 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 (4155 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	NM_001136018.4	MANE Select	c.-5-3071C>T		intron	N/A	NP_001129490.1
	EPHX1	NM_000120.4		c.-6+110C>T		intron	N/A	NP_000111.1
	EPHX1	NM_001291163.2		c.-5-3071C>T		intron	N/A	NP_001278092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	ENST00000272167.10	TSL:1 MANE Select	c.-5-3071C>T		intron	N/A	ENSP00000272167.5
	EPHX1	ENST00000366837.5	TSL:1	c.-6+110C>T		intron	N/A	ENSP00000355802.4
	EPHX1	ENST00000614058.4	TSL:1	c.-5-3071C>T		intron	N/A	ENSP00000480004.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32618 AN: 152046 Hom.: 4155 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.192 AC: 5 AN: 26 Hom.: 1 AF XY: 0.167 AC XY: 4 AN XY: 24

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.214 AC: 3 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.214 AC: 32612 AN: 152164 Hom.: 4155 Cov.: 32 AF XY: 0.216 AC XY: 16078 AN XY: 74392

African (AFR) AF: 0.0809 AC: 3361 AN: 41532

American (AMR) AF: 0.237 AC: 3618 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1693 AN: 5150

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4822

European-Finnish (FIN) AF: 0.224 AC: 2371 AN: 10598

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18139 AN: 67978

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.250 Hom.: 16661

Bravo AF: 0.207

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		-0.36
PromoterAI		0.0033	Neutral
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: rs1877724; hg19: chr1-226013355;