rs868966

Positions:

• chr1-225818396-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136018.4(EPHX1):​c.-6+8227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,006 control chromosomes in the GnomAD database, including 23,296 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 0.55 (23296 hom., cov: 31)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.-6+8227G>A		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.-6+8227G>A		intron_variant		1	NM_001136018.4	P1
EPHX1	ENST00000614058.4	c.-6+7781G>A		intron_variant		1		P1
EPHX1	ENST00000448202.5	c.-6+7781G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83859 AN: 151888 Hom.: 23282 Cov.: 31

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.552 AC: 83920 AN: 152006 Hom.: 23296 Cov.: 31 AF XY: 0.552 AC XY: 40986 AN XY: 74294

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.521

Alfa AF: 0.543 Hom.: 15846

Bravo AF: 0.555

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs868966; hg19: chr1-226006098;