18-45879182-A-G

Variant names:

• chr18-45879182-A-G
• rs34545102
• NM_020964.3:c.5700T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020964.3(EPG5):​c.5700T>C​(p.Phe1900Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,613,714 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (28 hom.)
• Consequence: EPG5 NM_020964.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Vici syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 18-45879182-A-G is Benign according to our data. Variant chr18-45879182-A-G is described in ClinVar as Benign. ClinVar VariationId is 466259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1868/152322) while in subpopulation AFR AF = 0.0418 (1737/41562). AF 95% confidence interval is 0.0402. There are 38 homozygotes in GnomAd4. There are 878 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020964.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	NM_020964.3	MANE Select	c.5700T>C	p.Phe1900Phe	synonymous	Exon 33 of 44	NP_066015.2
	EPG5	NM_001410859.1		c.5700T>C	p.Phe1900Phe	synonymous	Exon 33 of 44	NP_001397788.1
	EPG5	NM_001410858.1		c.5700T>C	p.Phe1900Phe	synonymous	Exon 33 of 44	NP_001397787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPG5	ENST00000282041.11	TSL:1 MANE Select	c.5700T>C	p.Phe1900Phe	synonymous	Exon 33 of 44	ENSP00000282041.4
	EPG5	ENST00000587884.2	TSL:1	n.*1440T>C		non_coding_transcript_exon	Exon 34 of 45	ENSP00000466990.2
	EPG5	ENST00000590884.6	TSL:1	n.*295T>C		non_coding_transcript_exon	Exon 33 of 42	ENSP00000466403.2

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1867 AN: 152204 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00308 AC: 766 AN: 249010 AF XY: 0.00226

Gnomad AFR exome AF: 0.0419

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000239

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00132 AC: 1930 AN: 1461392 Hom.: 28 Cov.: 31 AF XY: 0.00114 AC XY: 828 AN XY: 727032

African (AFR) AF: 0.0423 AC: 1412 AN: 33380

American (AMR) AF: 0.00269 AC: 120 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00348 AC: 20 AN: 5754

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1111930

Other (OTH) AF: 0.00353 AC: 213 AN: 60362

GnomAD4 genome AF: 0.0123 AC: 1868 AN: 152322 Hom.: 38 Cov.: 32 AF XY: 0.0118 AC XY: 878 AN XY: 74486

African (AFR) AF: 0.0418 AC: 1737 AN: 41562

American (AMR) AF: 0.00594 AC: 91 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00600 Hom.: 9

Bravo AF: 0.0142

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Vici syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.65
PhyloP100		2.7
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs34545102; hg19: chr18-43459147;