rs1042064

chr8-27544615-T-C

Variant summary

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

The NM_001979.6(EPHX2):c.*93T>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 0.296 in 1,269,652 control chromosomes in the GnomAD database, including 60,224 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 0.37 (12623 hom., cov: 31)
  • Exomes 𝑓: 0.29 (47601 hom.)
• Consequence: EPHX2 NM_001979.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX2	NM_001979.6	c.*93T>C		3_prime_UTR_variant	19/19	ENST00000521400.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX2	ENST00000521400.6	c.*93T>C		3_prime_UTR_variant	19/19	1	NM_001979.6	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56781 AN: 151898 Hom.: 12608 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.285 AC: 318767 AN: 1117636 Hom.: 47601 Cov.: 15 AF XY: 0.284 AC XY: 160167 AN XY: 564928

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.374 AC: 56840 AN: 152016 Hom.: 12623 Cov.: 31 AF XY: 0.369 AC XY: 27441 AN XY: 74300

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.351

Alfa AF: 0.278 Hom.: 12526

Bravo AF: 0.384

Asia WGS AF: 0.357 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.66

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: rs1042064; hg19: chr8-27402132; COSMIC: COSV66843828;