rs2285507

Positions:

• chr7-93359916-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017667.4(VPS50):​c.*1480G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,996 control chromosomes in the GnomAD database, including 6,749 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 0.29 (6749 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: VPS50 NM_017667.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS50	NM_017667.4	c.*1480G>A		3_prime_UTR_variant	28/28	ENST00000305866.10
VPS50	NM_001257998.2	c.*1480G>A		3_prime_UTR_variant	29/29
VPS50	XM_011516395.3	c.*1480G>A		3_prime_UTR_variant	27/27
VPS50	XM_024446826.2	c.*1480G>A		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS50	ENST00000305866.10	c.*1480G>A		3_prime_UTR_variant	28/28	1	NM_017667.4	P1
VPS50	ENST00000544910.5	c.*1480G>A		3_prime_UTR_variant	29/29	2
VPS50	ENST00000649152.1	c.*4298G>A		3_prime_UTR_variant, NMD_transcript_variant	29/29

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44352 AN: 151870 Hom.: 6727 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.292 AC: 44417 AN: 151988 Hom.: 6749 Cov.: 32 AF XY: 0.287 AC XY: 21316 AN XY: 74270

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.313

Alfa AF: 0.290 Hom.: 8705

Bravo AF: 0.300

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2285507; hg19: chr7-92989228;