dbSNP rs2285507: VPS50:c.*1480G>A (chr7-93359916-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

6 publications found

Variant links:

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

VPS50 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS50	NM_017667.4	MANE Select	c.*1480G>A		3_prime_UTR	Exon 28 of 28	NP_060137.2
	VPS50	NM_001257998.2		c.*1480G>A		3_prime_UTR	Exon 29 of 29	NP_001244927.1	Q96JG6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS50	ENST00000305866.10	TSL:1 MANE Select	c.*1480G>A	3_prime_UTR	Exon 28 of 28	ENSP00000307666.5	Q96JG6-1
VPS50	ENST00000544910.5	TSL:2	c.*1480G>A	3_prime_UTR	Exon 29 of 29	ENSP00000443104.1	Q96JG6-3
VPS50	ENST00000963423.1		c.*1480G>A	3_prime_UTR	Exon 27 of 27	ENSP00000633482.1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44352

AN:

151870

Hom.:

6727

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.292

AC:

44417

AN:

151988

Hom.:

6749

Cov.:

AF XY:

0.287

AC XY:

21316

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.354

AC:

14645

AN:

41414

American (AMR)

AF:

0.263

AC:

4016

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1473

AN:

3464

East Asian (EAS)

AF:

0.215

AC:

1117

AN:

5184

South Asian (SAS)

AF:

0.299

AC:

1440

AN:

4818

European-Finnish (FIN)

AF:

0.175

AC:

1850

AN:

10582

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18874

AN:

67960

Other (OTH)

AF:

0.313

AC:

658

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1562

3125

4687

6250

7812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.292

Hom.:

11134

Bravo

AF:

0.300

Asia WGS

AF:

0.260

AC:

903

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.62

PhyloP100

-0.034

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over