18-45865765-CAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chr18-45865765-C-CAAAAAAAAA
• rs11333207
• NM_020964.3:c.6622-15_6622-7dupTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_020964.3(EPG5):​c.6622-15_6622-7dupTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,411,546 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: EPG5 NM_020964.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.327

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-45865765-C-CAAAAAAAAA is Benign according to our data. Variant chr18-45865765-C-CAAAAAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1651997.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00078 (80/102562) while in subpopulation AFR AF= 0.00302 (76/25194). AF 95% confidence interval is 0.00247. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-15_6622-7dupTTTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	ENST00000282041.11	NP_066015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11	c.6622-7_6622-6insTTTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4

Frequencies

GnomAD3 genomes AF: 0.000780 AC: 80 AN: 102552 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000642 AC: 84 AN: 1308984 Hom.: 0 Cov.: 0 AF XY: 0.0000602 AC XY: 39 AN XY: 647394

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.000195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000302

Gnomad4 OTH exome AF: 0.000184

GnomAD4 genome AF: 0.000780 AC: 80 AN: 102562 Hom.: 0 Cov.: 25 AF XY: 0.000832 AC XY: 41 AN XY: 49282

Gnomad4 AFR AF: 0.00302

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000160

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

EPG5-related disorder Benign:1

Jun 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Vici syndrome Benign:1

Mar 16, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11333207; hg19: chr18-43445730;