NM_001979.6:c.*455C>T

Variant names:

• chr8-27544977-C-T
• rs4149259
• NM_001979.6:c.*455C>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.*455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 185,498 control chromosomes in the GnomAD database, including 6,683 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 0.25 (6056 hom., cov: 32)
  • Exomes 𝑓: 0.17 (627 hom.)
• Consequence: EPHX2 NM_001979.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 18 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001979.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX2	NM_001979.6	MANE Select	c.*455C>T		3_prime_UTR	Exon 19 of 19	NP_001970.2
	EPHX2	NM_001256482.2		c.*455C>T		3_prime_UTR	Exon 19 of 19	NP_001243411.1
	EPHX2	NM_001256484.2		c.*455C>T		3_prime_UTR	Exon 19 of 19	NP_001243413.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX2	ENST00000521400.6	TSL:1 MANE Select	c.*455C>T		3_prime_UTR	Exon 19 of 19	ENSP00000430269.1
	EPHX2	ENST00000850871.1		n.1589+733C>T		intron	N/A	ENSP00000520956.1
	EPHX2	ENST00000518379.5	TSL:5	c.*455C>T		downstream_gene	N/A	ENSP00000427956.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37561 AN: 151952 Hom.: 6036 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.170 AC: 5667 AN: 33426 Hom.: 627 Cov.: 0 AF XY: 0.171 AC XY: 2988 AN XY: 17442

African (AFR) AF: 0.522 AC: 402 AN: 770

American (AMR) AF: 0.138 AC: 445 AN: 3216

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 136 AN: 642

East Asian (EAS) AF: 0.200 AC: 372 AN: 1860

South Asian (SAS) AF: 0.186 AC: 709 AN: 3802

European-Finnish (FIN) AF: 0.118 AC: 143 AN: 1210

Middle Eastern (MID) AF: 0.200 AC: 24 AN: 120

European-Non Finnish (NFE) AF: 0.155 AC: 3137 AN: 20230

Other (OTH) AF: 0.190 AC: 299 AN: 1576

GnomAD4 genome AF: 0.247 AC: 37617 AN: 152072 Hom.: 6056 Cov.: 32 AF XY: 0.244 AC XY: 18103 AN XY: 74336

African (AFR) AF: 0.460 AC: 19086 AN: 41454

American (AMR) AF: 0.180 AC: 2747 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.193 AC: 990 AN: 5142

South Asian (SAS) AF: 0.199 AC: 960 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10592

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10960 AN: 67976

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.188 Hom.: 5457

Bravo AF: 0.259

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.63
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4149259; hg19: chr8-27402494;