rs2740168

Positions:

• chr1-225833287-G-A
• chr1-225833287-G-T

Variant summary

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

The NM_001136018.4(EPHX1):​c.364+1328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,182 control chromosomes in the GnomAD database, including 15,058 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 0.43 (15058 hom., cov: 33)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX1	NM_001136018.4	c.364+1328G>A		intron_variant		ENST00000272167.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX1	ENST00000272167.10	c.364+1328G>A		intron_variant		1	NM_001136018.4	P1
EPHX1	ENST00000366837.5	c.364+1328G>A		intron_variant		1		P1
EPHX1	ENST00000614058.4	c.364+1328G>A		intron_variant		1		P1
EPHX1	ENST00000448202.5	c.364+1328G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66103 AN: 152064 Hom.: 15019 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.435 AC: 66186 AN: 152182 Hom.: 15058 Cov.: 33 AF XY: 0.431 AC XY: 32046 AN XY: 74386

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.408

Alfa AF: 0.392 Hom.: 21971

Bravo AF: 0.441

Asia WGS AF: 0.485 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.33

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: rs2740168; hg19: chr1-226020988;