rs2071575

Positions:

• chr8-27540915-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.1379+259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,130 control chromosomes in the GnomAD database, including 17,495 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 0.43 (17495 hom., cov: 32)
• Consequence: EPHX2 NM_001979.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX2	NM_001979.6	c.1379+259T>C		intron_variant		ENST00000521400.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX2	ENST00000521400.6	c.1379+259T>C		intron_variant		1	NM_001979.6	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64724 AN: 152012 Hom.: 17452 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64812 AN: 152130 Hom.: 17495 Cov.: 32 AF XY: 0.419 AC XY: 31195 AN XY: 74364

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.413

Alfa AF: 0.300 Hom.: 9352

Bravo AF: 0.444

Asia WGS AF: 0.366 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.61

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: rs2071575; hg19: chr8-27398432;