rs3753661

Positions:

• chr1-225826641-T-G

Variant summary

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

The NM_001136018.4(EPHX1):​c.-5-2084T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 151,966 control chromosomes in the GnomAD database, including 686 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 0.080 (686 hom., cov: 31)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.-5-2084T>G		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.-5-2084T>G		intron_variant		1	NM_001136018.4	P1
EPHX1	ENST00000366837.5	c.-6+1097T>G		intron_variant		1		P1
EPHX1	ENST00000614058.4	c.-5-2084T>G		intron_variant		1		P1
EPHX1	ENST00000448202.5	c.-5-2084T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12171 AN: 151848 Hom.: 675 Cov.: 31

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0803 AC: 12201 AN: 151966 Hom.: 686 Cov.: 31 AF XY: 0.0837 AC XY: 6220 AN XY: 74274

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0917 Hom.: 1619

Bravo AF: 0.0816

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.45

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: rs3753661; hg19: chr1-226014342;