Variant chr18-45865765-C-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000282041.11(EPG5):c.6622-7_6622-6insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,378,268 control chromosomes in the GnomAD database, including 258 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 227 hom., cov: 25)

Exomes 𝑓: 0.086 ( 31 hom. )

Consequence

EPG5
ENST00000282041.11 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.327

Variant links:

Genes affected

EPG5 (HGNC:29331): (ectopic P-granules 5 autophagy tethering factor) This gene encodes a large coiled coil domain-containing protein that functions in autophagy during starvation conditions. Mutations in this gene cause Vici syndrome. [provided by RefSeq, Aug 2015]

EPG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 18-45865765-C-CA is Benign according to our data. Variant chr18-45865765-C-CA is described in ClinVar as [Benign]. Clinvar id is 769442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3 linkuse as main transcript	c.6622-7_6622-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000282041.11	NP_066015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11 linkuse as main transcript	c.6622-7_6622-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020964.3	ENSP00000282041	P4	Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0748

AC:

7663

AN:

102444

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0564

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.00752

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0962

GnomAD4 exome

AF:

0.0863

AC:

110101

AN:

1275814

Hom.:

Cov.:

AF XY:

0.0841

AC XY:

53074

AN XY:

630982

show subpopulations

Gnomad4 AFR exome

AF:

0.0507

Gnomad4 AMR exome

AF:

0.0364

Gnomad4 ASJ exome

AF:

0.0544

Gnomad4 EAS exome

AF:

0.0227

Gnomad4 SAS exome

AF:

0.0437

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.0961

Gnomad4 OTH exome

AF:

0.0773

GnomAD4 genome

AF:

0.0748

AC:

7665

AN:

102454

Hom.:

227

Cov.:

AF XY:

0.0719

AC XY:

3541

AN XY:

49226

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.0564

Gnomad4 ASJ

AF:

0.0645

Gnomad4 EAS

AF:

0.00755

Gnomad4 SAS

AF:

0.0254

Gnomad4 FIN

AF:

0.0907

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0951

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 01, 2019	- -

Vici syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over