rs2071575

Variant names:

• chr8-27540915-T-C
• rs2071575
• NM_001979.6:c.1379+259T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• hypercholesterolemia, familial, 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.1379+259T>C		intron_variant	Intron 15 of 18	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.1379+259T>C		intron_variant	Intron 15 of 18	1	NM_001979.6	ENSP00000430269.1

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

African (AFR) AF: 0.773 AC: 32094 AN: 41536

American (AMR) AF: 0.318 AC: 4853 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1921 AN: 5180

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2712 AN: 10586

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19397 AN: 67962

Other (OTH) AF: 0.413 AC: 873 AN: 2112

Alfa AF: 0.317 Hom.: 13720

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
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071575; hg19: chr8-27398432;