NM_001979.6:c.946-1238C>T

Variant names:

• chr8-27519645-C-T
• rs4149244
• NM_001979.6:c.946-1238C>T

Variant summary

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

The NM_001979.6(EPHX2):​c.946-1238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 152,268 control chromosomes in the GnomAD database, including 559 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 0.076 (559 hom., cov: 32)
• Consequence: EPHX2 NM_001979.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.946-1238C>T		intron_variant	Intron 9 of 18	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.946-1238C>T		intron_variant	Intron 9 of 18	1	NM_001979.6	ENSP00000430269.1

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11580 AN: 152148 Hom.: 557 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0948

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

GnomAD4 genome AF: 0.0761 AC: 11588 AN: 152268 Hom.: 559 Cov.: 32 AF XY: 0.0766 AC XY: 5705 AN XY: 74474

African (AFR) AF: 0.106 AC: 4413 AN: 41538

American (AMR) AF: 0.0548 AC: 838 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3470

East Asian (EAS) AF: 0.143 AC: 742 AN: 5188

South Asian (SAS) AF: 0.132 AC: 635 AN: 4822

European-Finnish (FIN) AF: 0.0458 AC: 486 AN: 10612

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3754 AN: 68020

Other (OTH) AF: 0.0929 AC: 196 AN: 2110

Alfa AF: 0.0632 Hom.: 597

Bravo AF: 0.0763

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.19
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: rs4149244; hg19: chr8-27377162; COSMIC: COSV66846173;