Genetic Variant NM_017667.4:c.2058+2275G>T (chr7-93336472-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017667.4(VPS50):c.2058+2275G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 152,212 control chromosomes in the GnomAD database, including 69 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 0.024 ( 69 hom., cov: 32)

Consequence

VPS50
NM_017667.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.188

Publications

1 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: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics
hydrocephalus
Inheritance: AR Classification: LIMITED Submitted by: LiferaOmics

VPS50 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017667.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0816 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.2058+2275G>T		intron	N/A	NP_060137.2
	VPS50	NM_001257998.2		c.1968+2275G>T		intron	N/A	NP_001244927.1	Q96JG6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS50	ENST00000305866.10	TSL:1 MANE Select	c.2058+2275G>T	intron	N/A	ENSP00000307666.5	Q96JG6-1
VPS50	ENST00000441602.5	TSL:1	n.*1831+2275G>T	intron	N/A	ENSP00000415809.1	F2Z3F0
VPS50	ENST00000471188.5	TSL:1	n.1564-4126G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3686

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0890

Gnomad SAS

AF:

0.0413

Gnomad FIN

AF:

0.00802

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0224

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

GnomAD4 genome

AF:

0.0242

AC:

3687

AN:

152212

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1824

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0447

AC:

1858

AN:

41538

American (AMR)

AF:

0.0148

AC:

226

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3472

East Asian (EAS)

AF:

0.0883

AC:

457

AN:

5178

South Asian (SAS)

AF:

0.0413

AC:

199

AN:

4820

European-Finnish (FIN)

AF:

0.00802

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

732

AN:

68002

Other (OTH)

AF:

0.0232

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

182

364

547

729

911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0155

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.0680

AC:

236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

(source)

DANN

Benign

0.68

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over