rs4149259

Positions:

• chr8-27544977-C-T

Variant summary

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

The NM_001979.6(EPHX2):​c.*455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 185,498 control chromosomes in the GnomAD database, including 6,683 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 (6056 hom., cov: 32)
  • Exomes 𝑓: 0.17 (627 hom.)
• Consequence: EPHX2 NM_001979.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

EPHX2 (HGNC:3402): (epoxide hydrolase 2) This gene encodes a member of the epoxide hydrolase family. The protein, found in both the cytosol and peroxisomes, binds to specific epoxides and converts them to the corresponding dihydrodiols. Mutations in this gene have been associated with familial hypercholesterolemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX2	NM_001979.6	c.*455C>T		3_prime_UTR_variant	19/19	ENST00000521400.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX2	ENST00000521400.6	c.*455C>T		3_prime_UTR_variant	19/19	1	NM_001979.6	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37561 AN: 151952 Hom.: 6036 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.170 AC: 5667 AN: 33426 Hom.: 627 Cov.: 0 AF XY: 0.171 AC XY: 2988 AN XY: 17442

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.247 AC: 37617 AN: 152072 Hom.: 6056 Cov.: 32 AF XY: 0.244 AC XY: 18103 AN XY: 74336

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.250

Alfa AF: 0.178 Hom.: 3715

Bravo AF: 0.259

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4149259; hg19: chr8-27402494;