18-45865765-CAAAAAAA-CAAAAAAAAAAAAAAAAAAA

Position:

• chr18-45865765-CAAAAAAA-CAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP6_Very_Strong BS1

The ENST00000282041.11(EPG5):​c.6622-7_6622-6insTTTTTTTTTTTT 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 0.000288 in 1,411,396 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 25)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: EPG5 ENST00000282041.11 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts 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 Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-45865765-C-CAAAAAAAAAAAA is Benign according to our data. Variant chr18-45865765-C-CAAAAAAAAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1127228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00254 (260/102452) while in subpopulation AFR AF= 0.00964 (242/25094). AF 95% confidence interval is 0.00865. There are 1 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3	c.6622-7_6622-6insTTTTTTTTTTTT		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	c.6622-7_6622-6insTTTTTTTTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020964.3	ENSP00000282041	P4

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 260 AN: 102440 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.00966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000616

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00279

GnomAD4 exome AF: 0.000112 AC: 146 AN: 1308944 Hom.: 0 Cov.: 0 AF XY: 0.000103 AC XY: 67 AN XY: 647370

Gnomad4 AFR exome AF: 0.00181

Gnomad4 AMR exome AF: 0.000585

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000734

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000584

Gnomad4 OTH exome AF: 0.000184

GnomAD4 genome AF: 0.00254 AC: 260 AN: 102452 Hom.: 1 Cov.: 25 AF XY: 0.00234 AC XY: 115 AN XY: 49238

Gnomad4 AFR AF: 0.00964

Gnomad4 AMR AF: 0.000616

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00278

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 19, 2021

See Variant Classification Assertion Criteria. -

Vici syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

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;