1-225827415-A-G

Position:

• chr1-225827415-A-G

Variant summary

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

The NM_001136018.4(EPHX1):​c.-5-1310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,132 control chromosomes in the GnomAD database, including 39,280 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 0.70 (39280 hom., cov: 32)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852

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 (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.-5-1310A>G		intron_variant		ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.-5-1310A>G		intron_variant		1	NM_001136018.4	ENSP00000272167	P1
EPHX1	ENST00000366837.5	c.-5-1310A>G		intron_variant		1		ENSP00000355802	P1
EPHX1	ENST00000614058.4	c.-5-1310A>G		intron_variant		1		ENSP00000480004	P1
EPHX1	ENST00000448202.5	c.-5-1310A>G		intron_variant		2		ENSP00000408469

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106310 AN: 152014 Hom.: 39258 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.699 AC: 106365 AN: 152132 Hom.: 39280 Cov.: 32 AF XY: 0.706 AC XY: 52529 AN XY: 74382

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.724

Alfa AF: 0.776 Hom.: 95316

Bravo AF: 0.683

Asia WGS AF: 0.895 AC: 3111 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	1.1
DANN	Benign	0.54

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: rs2671272; hg19: chr1-226015116;