rs3738042

Variant names:

• chr1-225825687-G-A
• rs3738042
• NM_001136018.4:c.-5-3038G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-225825687-G-A
• chr1-225825687-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136018.4(EPHX1):​c.-5-3038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,222 control chromosomes in the GnomAD database, including 5,103 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 0.25 (5102 hom., cov: 32)
  • Exomes 𝑓: 0.28 (1 hom.)
• Consequence: EPHX1 NM_001136018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 11 publications found

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]

EPHX1 Gene-Disease associations (from GenCC):

• familial hypercholanemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136018.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	NM_001136018.4	MANE Select	c.-5-3038G>A		intron	N/A	NP_001129490.1	R4SBI6
	EPHX1	NM_000120.4		c.-6+143G>A		intron	N/A	NP_000111.1	R4SBI6
	EPHX1	NM_001291163.2		c.-5-3038G>A		intron	N/A	NP_001278092.1	P07099

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX1	ENST00000272167.10	TSL:1 MANE Select	c.-5-3038G>A		intron	N/A	ENSP00000272167.5	P07099
	EPHX1	ENST00000366837.5	TSL:1	c.-6+143G>A		intron	N/A	ENSP00000355802.4	P07099
	EPHX1	ENST00000614058.4	TSL:1	c.-5-3038G>A		intron	N/A	ENSP00000480004.1	P07099

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37787 AN: 152072 Hom.: 5104 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.281 AC: 9 AN: 32 Hom.: 1 AF XY: 0.250 AC XY: 6 AN XY: 24

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.222 AC: 4 AN: 18

Other (OTH) AF: 0.333 AC: 2 AN: 6

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0239849), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.248 AC: 37791 AN: 152190 Hom.: 5102 Cov.: 32 AF XY: 0.249 AC XY: 18504 AN XY: 74398

African (AFR) AF: 0.147 AC: 6125 AN: 41550

American (AMR) AF: 0.263 AC: 4016 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3472

East Asian (EAS) AF: 0.157 AC: 812 AN: 5170

South Asian (SAS) AF: 0.215 AC: 1040 AN: 4826

European-Finnish (FIN) AF: 0.330 AC: 3494 AN: 10592

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20575 AN: 67976

Other (OTH) AF: 0.263 AC: 556 AN: 2114

Alfa AF: 0.287 Hom.: 11052

Bravo AF: 0.238

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.43
PhyloP100		-0.89
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3738042; hg19: chr1-226013388;