rs4614

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021729.6(VPS11):c.*38A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,605,874 control chromosomes in the GnomAD database, including 124,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12576 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112329 hom. )

Consequence

VPS11
NM_021729.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.136

Publications

44 publications found

Variant links:

Genes affected

VPS11 (HGNC:14583): (VPS11 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps11 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

VPS11 Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 12
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

VPS11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4564395E-4).

BP6

Variant 11-119081661-A-G is Benign according to our data. Variant chr11-119081661-A-G is described in ClinVar as Benign. ClinVar VariationId is 1684212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS11	NM_021729.6 link	c.*38A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000621676.5	NP_068375.3	Q9H270A0A087WXL6B7Z879

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS11	ENST00000621676.5 link	c.*38A>G	3_prime_UTR_variant	Exon 16 of 16	1	NM_021729.6	ENSP00000481126.1	A0A087WXL6
VPS11	ENST00000524454.1 link	n.322A>G	non_coding_transcript_exon_variant	Exon 2 of 2	2
VPS11	ENST00000622309.4 link	n.3049A>G	non_coding_transcript_exon_variant	Exon 13 of 13	5
VPS11	ENST00000614944.4 link	c.*38A>G	3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000481807.1	B7Z879

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60682

AN:

151976

Hom.:

12567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.414

GnomAD2 exomes

AF:

0.357

AC:

83663

AN:

234180

AF XY:

0.362

show subpopulations

Gnomad AFR exome

AF:

0.479

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.389

AC:

565556

AN:

1453780

Hom.:

112329

Cov.:

AF XY:

0.389

AC XY:

280853

AN XY:

722272

show subpopulations

African (AFR)

AF:

0.478

AC:

15922

AN:

33314

American (AMR)

AF:

0.285

AC:

12414

AN:

43490

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

10760

AN:

25924

East Asian (EAS)

AF:

0.141

AC:

5582

AN:

39520

South Asian (SAS)

AF:

0.360

AC:

30953

AN:

85868

European-Finnish (FIN)

AF:

0.290

AC:

15249

AN:

52672

Middle Eastern (MID)

AF:

0.399

AC:

2264

AN:

5670

European-Non Finnish (NFE)

AF:

0.406

AC:

449064

AN:

1107240

Other (OTH)

AF:

0.389

AC:

23348

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

19231

38463

57694

76926

96157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13830

27660

41490

55320

69150

<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:

0.399

AC:

60716

AN:

152094

Hom.:

12576

Cov.:

AF XY:

0.391

AC XY:

29053

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.476

AC:

19742

AN:

41504

American (AMR)

AF:

0.347

AC:

5307

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1406

AN:

3464

East Asian (EAS)

AF:

0.174

AC:

897

AN:

5166

South Asian (SAS)

AF:

0.351

AC:

1694

AN:

4822

European-Finnish (FIN)

AF:

0.283

AC:

2996

AN:

10588

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.402

AC:

27288

AN:

67950

Other (OTH)

AF:

0.415

AC:

874

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1858

3716

5575

7433

9291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.398

Hom.:

14493

Bravo

AF:

0.404

TwinsUK

AF:

0.398

AC:

1476

ALSPAC

AF:

0.389

AC:

1498

ESP6500AA

AF:

0.470

AC:

1924

ESP6500EA

AF:

0.407

AC:

3397

ExAC

AF:

0.357

AC:

43145

Asia WGS

AF:

0.278

AC:

966

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dystonia 32

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hypomyelinating leukodystrophy 12

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0061

FATHMM_MKL

Benign

0.028

MetaRNN

Benign

0.00015

PhyloP100

-0.14

Sift4G

Benign

0.061

Vest4

0.020

GERP RS

-1.9

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over