8-27544557-A-G

Position:

• chr8-27544557-A-G

Variant summary

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

The ENST00000521400.6(EPHX2):​c.*35A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,607,632 control chromosomes in the GnomAD database, including 75,683 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 0.38 (13790 hom., cov: 32)
  • Exomes 𝑓: 0.28 (61893 hom.)
• Consequence: EPHX2 ENST00000521400.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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 = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.*35A>G		3_prime_UTR_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.*35A>G		3_prime_UTR_variant	19/19	1	NM_001979.6	ENSP00000430269	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58250 AN: 152010 Hom.: 13767 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.363

GnomAD3 exomes AF: 0.299 AC: 75005 AN: 250930 Hom.: 12784 AF XY: 0.289 AC XY: 39244 AN XY: 135666

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: 0.287

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.283 AC: 411295 AN: 1455504 Hom.: 61893 Cov.: 31 AF XY: 0.281 AC XY: 203216 AN XY: 724388

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.383 AC: 58317 AN: 152128 Hom.: 13790 Cov.: 32 AF XY: 0.378 AC XY: 28137 AN XY: 74358

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.358

Alfa AF: 0.276 Hom.: 7951

Bravo AF: 0.396

Asia WGS AF: 0.359 AC: 1251 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	0.14
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1042032; hg19: chr8-27402074; COSMIC: COSV66844751;