8-27491271-C-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001979.6(EPHX2):c.63C>A(p.Gly21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,578,248 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (35 hom.)
• Consequence: EPHX2 NM_001979.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.511

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 8-27491271-C-A is Benign according to our data. Variant chr8-27491271-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 779344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.511 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHX2	NM_001979.6	c.63C>A	p.Gly21=	synonymous_variant	1/19	ENST00000521400.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHX2	ENST00000521400.6	c.63C>A	p.Gly21=	synonymous_variant	1/19	1	NM_001979.6	P1

Frequencies

GnomAD3 genomes AF: 0.00455 AC: 692 AN: 152240 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00664

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00441 AC: 840 AN: 190438 Hom.: 8 AF XY: 0.00455 AC XY: 486 AN XY: 106700

Gnomad AFR exome AF: 0.00122

Gnomad AMR exome AF: 0.00262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000960

Gnomad FIN exome AF: 0.00929

Gnomad NFE exome AF: 0.00706

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00663 AC: 9451 AN: 1425890 Hom.: 35 Cov.: 31 AF XY: 0.00641 AC XY: 4543 AN XY: 708716

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00243

Gnomad4 ASJ exome AF: 0.0000394

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000946

Gnomad4 FIN exome AF: 0.00913

Gnomad4 NFE exome AF: 0.00774

Gnomad4 OTH exome AF: 0.00581

GnomAD4 genome AF: 0.00454 AC: 692 AN: 152358 Hom.: 2 Cov.: 33 AF XY: 0.00499 AC XY: 372 AN XY: 74504

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.00664

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00521 Hom.: 2

Bravo AF: 0.00378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	EPHX2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	8.9
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs2234912; hg19: chr8-27348788; COSMIC: COSV66844561; COSMIC: COSV66844561;