18-45800871-A-G

Variant names:

• chr18-45800871-A-G
• rs559774
• NM_001410858.1:c.7577T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001410858.1(EPG5):​c.7577T>C​(p.Phe2526Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,152 control chromosomes in the GnomAD database, including 44,659 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44659 hom., cov: 32)
• Consequence: EPG5 NM_001410858.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.744

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 18-45800871-A-G is Benign according to our data. Variant chr18-45800871-A-G is described in ClinVar as [Benign]. Clinvar id is 2687932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_001410858.1	c.7577T>C	p.Phe2526Ser	missense_variant	Exon 44 of 44		NP_001397787.1
EPG5	XM_047437703.1	c.7604T>C	p.Phe2535Ser	missense_variant	Exon 44 of 44		XP_047293659.1
EPG5	XM_047437704.1	c.7601T>C	p.Phe2534Ser	missense_variant	Exon 44 of 44		XP_047293660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000696483.1	c.7577T>C	p.Phe2526Ser	missense_variant	Exon 44 of 44			ENSP00000512657.1
EPG5	ENST00000696484.1	c.7462T>C	p.Leu2488Leu	synonymous_variant	Exon 43 of 43			ENSP00000512658.1
EPG5	ENST00000696481.1	n.4094T>C		non_coding_transcript_exon_variant	Exon 16 of 16
EPG5	ENST00000696491.1	n.160T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114821 AN: 152034 Hom.: 44601 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.736

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.755 AC: 114937 AN: 152152 Hom.: 44659 Cov.: 32 AF XY: 0.755 AC XY: 56182 AN XY: 74370

African (AFR) AF: 0.929 AC: 38607 AN: 41548

American (AMR) AF: 0.784 AC: 11985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2317 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4774 AN: 5176

South Asian (SAS) AF: 0.695 AC: 3353 AN: 4822

European-Finnish (FIN) AF: 0.681 AC: 7190 AN: 10554

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44523 AN: 67972

Other (OTH) AF: 0.733 AC: 1550 AN: 2116

Alfa AF: 0.684 Hom.: 17774

Bravo AF: 0.773

Asia WGS AF: 0.804 AC: 2798 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 90. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	9.9
DANN	Benign	0.37
PhyloP100		0.74

Splicing

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

Publications

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Other links and lift over

dbSNP: rs559774; hg19: chr18-43380836;