rs747276

Positions:

• chr8-27534103-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521400.6(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 ENST00000521400.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EPHX2	NM_001979.6	c.1171-2681G>C		intron_variant		ENST00000521400.6	NP_001970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHX2	ENST00000521400.6	c.1171-2681G>C		intron_variant		1	NM_001979.6	ENSP00000430269	P1

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

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.312

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs747276; hg19: chr8-27391620;