rs1126452

Positions:

• chr8-27544447-A-C

Variant summary

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

The NM_001979.6(EPHX2):​c.1593A>C​(p.Pro531Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,310 control chromosomes in the GnomAD database, including 75,909 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 0.38 (13745 hom., cov: 31)
  • Exomes 𝑓: 0.28 (62164 hom.)
• Consequence: EPHX2 NM_001979.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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]

EPHX2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.1593A>C	p.Pro531Pro	synonymous_variant	19/19	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.1593A>C	p.Pro531Pro	synonymous_variant	19/19	1	NM_001979.6	ENSP00000430269.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58130 AN: 151820 Hom.: 13722 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.299 AC: 74751 AN: 249976 Hom.: 12783 AF XY: 0.289 AC XY: 39144 AN XY: 135266

Gnomad AFR exome AF: 0.683

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.370

Gnomad SAS exome AF: 0.286

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.282 AC: 412691 AN: 1461372 Hom.: 62164 Cov.: 35 AF XY: 0.280 AC XY: 203837 AN XY: 727024

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.383 AC: 58197 AN: 151938 Hom.: 13745 Cov.: 31 AF XY: 0.378 AC XY: 28099 AN XY: 74274

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.357

Alfa AF: 0.277 Hom.: 14604

Bravo AF: 0.396

Asia WGS AF: 0.358 AC: 1249 AN: 3478

EpiCase AF: 0.258

EpiControl AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1126452; hg19: chr8-27401964; COSMIC: COSV66844933;