18-45800871-A-G

Position:

• chr18-45800871-A-G

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EPG5	NM_001410858.1	c.7577T>C	p.Phe2526Ser	missense_variant	44/44		NP_001397787.1
EPG5	XM_047437703.1	c.7604T>C	p.Phe2535Ser	missense_variant	44/44		XP_047293659.1
EPG5	XM_047437704.1	c.7601T>C	p.Phe2534Ser	missense_variant	44/44		XP_047293660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000696483.1	c.7577T>C	p.Phe2526Ser	missense_variant	44/44			ENSP00000512657
EPG5	ENST00000696484.1	c.7462T>C	p.Leu2488=	synonymous_variant	43/43			ENSP00000512658
EPG5	ENST00000696481.1	n.4094T>C		non_coding_transcript_exon_variant	16/16
EPG5	ENST00000696491.1	n.160T>C		non_coding_transcript_exon_variant	2/2

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

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.733

Alfa AF: 0.686 Hom.: 16012

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs559774; hg19: chr18-43380836;