rs2740171

Variant names:

• chr1-225837827-A-C
• rs2740171
• NM_001136018.4:c.365-827A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-225837827-A-C
• chr1-225837827-A-G
• chr1-225837827-A-T

Variant summary

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

The NM_001136018.4(EPHX1):​c.365-827A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,166 control chromosomes in the GnomAD database, including 43,472 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 0.75 (43472 hom., cov: 33)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.365-827A>C		intron_variant	Intron 3 of 8	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.365-827A>C		intron_variant	Intron 3 of 8	1	NM_001136018.4	ENSP00000272167.5
EPHX1	ENST00000366837.5	c.365-827A>C		intron_variant	Intron 3 of 8	1		ENSP00000355802.4
EPHX1	ENST00000614058.4	c.365-827A>C		intron_variant	Intron 3 of 8	1		ENSP00000480004.1
EPHX1	ENST00000448202.5	c.365-827A>C		intron_variant	Intron 3 of 3	2		ENSP00000408469.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114380 AN: 152048 Hom.: 43441 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.752 AC: 114462 AN: 152166 Hom.: 43472 Cov.: 33 AF XY: 0.758 AC XY: 56357 AN XY: 74398

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.751

Alfa AF: 0.761 Hom.: 42194

Bravo AF: 0.748

Asia WGS AF: 0.843 AC: 2932 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	0.64
DANN	Benign	0.43

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: rs2740171; hg19: chr1-226025528;