rs721619

Variant names:

• chr8-27524479-C-G
• rs721619
• NM_001979.6:c.1059-883C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001979.6(EPHX2):​c.1059-883C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,132 control chromosomes in the GnomAD database, including 5,579 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 0.26 (5579 hom., cov: 31)
• Consequence: EPHX2 NM_001979.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.1059-883C>G		intron_variant	Intron 11 of 18	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.1059-883C>G		intron_variant	Intron 11 of 18	1	NM_001979.6	ENSP00000430269.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39225 AN: 152014 Hom.: 5572 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.258 AC: 39245 AN: 152132 Hom.: 5579 Cov.: 31 AF XY: 0.256 AC XY: 19045 AN XY: 74376

African (AFR) AF: 0.134 AC: 5580 AN: 41538

American (AMR) AF: 0.299 AC: 4565 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1116 AN: 5180

South Asian (SAS) AF: 0.309 AC: 1488 AN: 4814

European-Finnish (FIN) AF: 0.261 AC: 2763 AN: 10582

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21661 AN: 67964

Other (OTH) AF: 0.280 AC: 591 AN: 2114

Alfa AF: 0.291 Hom.: 1039

Bravo AF: 0.256

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.45
PhyloP100		0.024
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: rs721619; hg19: chr8-27381996;