NM_017667.4:c.1855+3176T>C

Variant names:

• chr7-93314448-T-C
• rs2188404
• NM_017667.4:c.1855+3176T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017667.4(VPS50):​c.1855+3176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,962 control chromosomes in the GnomAD database, including 7,214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7214 hom., cov: 31)
• Consequence: VPS50 NM_017667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 5 publications found

Genes affected

VPS50 (HGNC:25956): (VPS50 subunit of EARP/GARPII complex) Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [provided by Alliance of Genome Resources, Apr 2022]

VPS50 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017667.4. 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
	VPS50	NM_017667.4	MANE Select	c.1855+3176T>C		intron	N/A	NP_060137.2
	VPS50	NM_001257998.2		c.1765+3176T>C		intron	N/A	NP_001244927.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS50	ENST00000305866.10	TSL:1 MANE Select	c.1855+3176T>C		intron	N/A	ENSP00000307666.5
	VPS50	ENST00000441602.5	TSL:1	n.*1628+3176T>C		intron	N/A	ENSP00000415809.1
	VPS50	ENST00000471188.5	TSL:1	n.1563+3176T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46173 AN: 151844 Hom.: 7199 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.304 AC: 46208 AN: 151962 Hom.: 7214 Cov.: 31 AF XY: 0.300 AC XY: 22271 AN XY: 74288

African (AFR) AF: 0.331 AC: 13704 AN: 41424

American (AMR) AF: 0.377 AC: 5748 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2083 AN: 5150

South Asian (SAS) AF: 0.252 AC: 1216 AN: 4820

European-Finnish (FIN) AF: 0.223 AC: 2360 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19320 AN: 67946

Other (OTH) AF: 0.284 AC: 599 AN: 2108

Alfa AF: 0.293 Hom.: 12737

Bravo AF: 0.322

Asia WGS AF: 0.311 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs2188404; hg19: chr7-92943760;