8-27508884-G-C

Variant names:

• chr8-27508884-G-C
• rs13262930
• NM_001979.6:c.660+1890G>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.660+1890G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 149,734 control chromosomes in the GnomAD database, including 17,136 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 0.42 (17136 hom., cov: 27)
• Consequence: EPHX2 NM_001979.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 10 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)

ENSG00000289323 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.660+1890G>C		intron_variant	Intron 5 of 18	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.660+1890G>C		intron_variant	Intron 5 of 18	1	NM_001979.6	ENSP00000430269.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 62564 AN: 149648 Hom.: 17091 Cov.: 27

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.418 AC: 62655 AN: 149734 Hom.: 17136 Cov.: 27 AF XY: 0.413 AC XY: 30090 AN XY: 72846

African (AFR) AF: 0.788 AC: 32073 AN: 40696

American (AMR) AF: 0.314 AC: 4704 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 993 AN: 3460

East Asian (EAS) AF: 0.364 AC: 1842 AN: 5058

South Asian (SAS) AF: 0.342 AC: 1612 AN: 4708

European-Finnish (FIN) AF: 0.230 AC: 2278 AN: 9886

Middle Eastern (MID) AF: 0.402 AC: 115 AN: 286

European-Non Finnish (NFE) AF: 0.266 AC: 18016 AN: 67676

Other (OTH) AF: 0.404 AC: 837 AN: 2072

Alfa AF: 0.332 Hom.: 1301

Bravo AF: 0.439

Asia WGS AF: 0.368 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.63
PhyloP100		-0.47
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: rs13262930; hg19: chr8-27366401;