8-27544615-T-C

Variant names:

• chr8-27544615-T-C
• rs1042064
• NM_001979.6:c.*93T>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.*93T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,269,652 control chromosomes in the GnomAD database, including 60,224 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 0.37 (12623 hom., cov: 31)
  • Exomes 𝑓: 0.29 (47601 hom.)
• Consequence: EPHX2 NM_001979.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 39 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 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.*93T>C		3_prime_UTR	Exon 19 of 19	NP_001970.2
	EPHX2	NR_182231.1		n.1793T>C		non_coding_transcript_exon	Exon 18 of 18
	EPHX2	NR_182232.1		n.1816T>C		non_coding_transcript_exon	Exon 18 of 18

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHX2	ENST00000521400.6	TSL:1 MANE Select	c.*93T>C		3_prime_UTR	Exon 19 of 19	ENSP00000430269.1
	EPHX2	ENST00000518379.5	TSL:5	c.*93T>C		3_prime_UTR	Exon 18 of 18	ENSP00000427956.1
	EPHX2	ENST00000380476.7	TSL:2	c.*93T>C		3_prime_UTR	Exon 19 of 19	ENSP00000369843.3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56781 AN: 151898 Hom.: 12608 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.285 AC: 318767 AN: 1117636 Hom.: 47601 Cov.: 15 AF XY: 0.284 AC XY: 160167 AN XY: 564928

African (AFR) AF: 0.630 AC: 16643 AN: 26434

American (AMR) AF: 0.271 AC: 11586 AN: 42700

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 5875 AN: 23746

East Asian (EAS) AF: 0.418 AC: 15687 AN: 37524

South Asian (SAS) AF: 0.285 AC: 22443 AN: 78660

European-Finnish (FIN) AF: 0.277 AC: 14614 AN: 52842

Middle Eastern (MID) AF: 0.262 AC: 914 AN: 3486

European-Non Finnish (NFE) AF: 0.269 AC: 216574 AN: 803718

Other (OTH) AF: 0.297 AC: 14431 AN: 48526

GnomAD4 genome AF: 0.374 AC: 56840 AN: 152016 Hom.: 12623 Cov.: 31 AF XY: 0.369 AC XY: 27441 AN XY: 74300

African (AFR) AF: 0.626 AC: 25963 AN: 41456

American (AMR) AF: 0.286 AC: 4373 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3472

East Asian (EAS) AF: 0.390 AC: 2013 AN: 5158

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4812

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10566

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18267 AN: 67964

Other (OTH) AF: 0.351 AC: 740 AN: 2110

Alfa AF: 0.297 Hom.: 31164

Bravo AF: 0.384

Asia WGS AF: 0.357 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		-0.53
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: rs1042064; hg19: chr8-27402132; COSMIC: COSV66843828;