Variant 18-45865765-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_020964.3(EPG5):c.6622-6G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,306,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0067 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPG5
NM_020964.3 splice_region, intron

Scores

Splicing: ADA: 0.00001476

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.245

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:

EPG5 (HGNC:):

EPG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Variant has high frequency in the AFR(0.00362458) population. However there is too low homozygotes in high coverage region: (expected more than 14, got 0).

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 18-45865765-C-A is Benign according to our data. Variant chr18-45865765-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 466262.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00666 (8710/1306956) while in subpopulation SAS AF= 0.0189 (1276/67662). AF 95% confidence interval is 0.018. There are 0 homozygotes in gnomad4_exome. There are 4857 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3 linkuse as main transcript	c.6622-6G>T		splice_region_variant, intron_variant		ENST00000282041.11	NP_066015.2	Q9HCE0-1Q9BTI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11 linkuse as main transcript	c.6622-6G>T		splice_region_variant, intron_variant		1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

392

AN:

101754

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.0103

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00169

Gnomad EAS

AF:

0.00201

Gnomad SAS

AF:

0.00220

Gnomad FIN

AF:

0.00786

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00666

AC:

8710

AN:

1306956

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

4857

AN XY:

646222

show subpopulations

Gnomad4 AFR exome

AF:

0.00809

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.00990

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0124

Gnomad4 NFE exome

AF:

0.00492

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00385

AC:

392

AN:

101764

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

204

AN XY:

48958

show subpopulations

Gnomad4 AFR

AF:

0.00428

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00169

Gnomad4 EAS

AF:

0.00202

Gnomad4 SAS

AF:

0.00221

Gnomad4 FIN

AF:

0.00786

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00729

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vici syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0080

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