rs747276

Variant names:

• chr8-27534103-G-C
• rs747276
• NM_001979.6:c.1171-2681G>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.1171-2681G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,090 control chromosomes in the GnomAD database, including 11,473 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 0.31 (11473 hom., cov: 32)
• Consequence: EPHX2 NM_001979.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.1171-2681G>C		intron_variant	Intron 12 of 18	ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.1171-2681G>C		intron_variant	Intron 12 of 18	1	NM_001979.6	ENSP00000430269.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47661 AN: 151970 Hom.: 11436 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.314 AC: 47739 AN: 152090 Hom.: 11473 Cov.: 32 AF XY: 0.308 AC XY: 22869 AN XY: 74366

African (AFR) AF: 0.678 AC: 28113 AN: 41466

American (AMR) AF: 0.217 AC: 3313 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3472

East Asian (EAS) AF: 0.180 AC: 932 AN: 5178

South Asian (SAS) AF: 0.202 AC: 975 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1453 AN: 10566

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11238 AN: 67992

Other (OTH) AF: 0.312 AC: 659 AN: 2112

Alfa AF: 0.231 Hom.: 949

Bravo AF: 0.333

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.45
PhyloP100		-0.0030
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: rs747276; hg19: chr8-27391620;