Variant rs114665741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000282041.11(EPG5):c.6516C>T(p.Tyr2172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,613,970 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 25 hom. )

Consequence

EPG5
ENST00000282041.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.824

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 18-45866903-G-A is Benign according to our data. Variant chr18-45866903-G-A is described in ClinVar as [Benign]. Clinvar id is 534617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.824 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00897 (1366/152280) while in subpopulation AFR AF= 0.0254 (1054/41556). AF 95% confidence interval is 0.0241. There are 14 homozygotes in gnomad4. There are 654 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3 linkuse as main transcript	c.6516C>T	p.Tyr2172=	synonymous_variant	38/44	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.6516C>T	p.Tyr2172=	synonymous_variant	38/44	1	NM_020964.3	ENSP00000282041	P4	Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1361

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00400

AC:

997

AN:

249512

Hom.:

AF XY:

0.00348

AC XY:

471

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.00698

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00594

GnomAD4 exome

AF:

0.00224

AC:

3276

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1616

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0267

Gnomad4 AMR exome

AF:

0.00693

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00537

GnomAD4 genome

AF:

0.00897

AC:

1366

AN:

152280

Hom.:

Cov.:

AF XY:

0.00878

AC XY:

654

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0254

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00165

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00261

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 23, 2020	- -

Vici syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.3

DANN

Benign

0.40

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