rs4653695

Positions:

• chr1-225845382-A-C
• chr1-225845382-A-G
• chr1-225845382-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136018.4(EPHX1):​c.*35A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,352,544 control chromosomes in the GnomAD database, including 9,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (934 hom., cov: 0)
  • Exomes 𝑓: 0.11 (8907 hom.)
• Consequence: EPHX1 NM_001136018.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.439

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-225845382-A-C is Benign according to our data. Variant chr1-225845382-A-C is described in ClinVar as [Benign]. Clinvar id is 1248948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX1	NM_001136018.4	c.*35A>C		3_prime_UTR_variant	9/9	ENST00000272167.10	NP_001129490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX1	ENST00000272167.10	c.*35A>C		3_prime_UTR_variant	9/9	1	NM_001136018.4	ENSP00000272167	P1
EPHX1	ENST00000366837.5	c.*35A>C		3_prime_UTR_variant	9/9	1		ENSP00000355802	P1
EPHX1	ENST00000614058.4	c.*35A>C		3_prime_UTR_variant	9/9	1		ENSP00000480004	P1
	ENST00000424332.1	n.43+1098T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 14003 AN: 50984 Hom.: 932 Cov.: 0

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.266

GnomAD3 exomes AF: 0.119 AC: 17748 AN: 148610 Hom.: 1536 AF XY: 0.109 AC XY: 8876 AN XY: 81160

Gnomad AFR exome AF: 0.0246

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.0963

Gnomad SAS exome AF: 0.0490

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.113 AC: 147549 AN: 1301506 Hom.: 8907 Cov.: 30 AF XY: 0.111 AC XY: 71045 AN XY: 641998

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.0660

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.0489

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.275 AC: 14016 AN: 51038 Hom.: 934 Cov.: 0 AF XY: 0.275 AC XY: 7109 AN XY: 25878

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.262

Alfa AF: 0.0975 Hom.: 1514

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.72

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: rs4653695; hg19: chr1-226033083;