ENST00000453601.5:n.225_227dupCCG

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The ENST00000453601.5(VLDLR-AS1):n.225_227dupCCG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.25 ( 5849 hom., cov: 0)

Exomes 𝑓: 0.29 ( 37238 hom. )

Consequence

VLDLR-AS1
ENST00000453601.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 2.20

Publications

3 publications found

Variant links:

Genes affected

VLDLR-AS1 (HGNC:49621): (VLDLR antisense RNA 1)

VLDLR-AS1 links:

VLDLR (HGNC:12698): (very low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq, Aug 2009]

VLDLR Gene-Disease associations (from GenCC):

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
cerebellar ataxia, intellectual disability, and dysequilibrium
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

VLDLR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 9-2622146-A-ACGG is Benign according to our data. Variant chr9-2622146-A-ACGG is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 287823.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VLDLR	NM_003383.5 link	c.-21_-19dupGGC		5_prime_UTR_variant	Exon 1 of 19	ENST00000382100.8	NP_003374.3	P98155-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VLDLR	ENST00000382100.8 link	c.-21_-19dupGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2		P98155-1

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38285

AN:

150414

Hom.:

5843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0966

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.0532

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.302

AC:

15122

AN:

50120

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.279

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.0615

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.293

AC:

361375

AN:

1234812

Hom.:

37238

Cov.:

AF XY:

0.296

AC XY:

179468

AN XY:

607236

show subpopulations

African (AFR)

AF:

0.0877

AC:

2252

AN:

25664

American (AMR)

AF:

0.248

AC:

5958

AN:

24044

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

6625

AN:

20164

East Asian (EAS)

AF:

0.0443

AC:

1321

AN:

29818

South Asian (SAS)

AF:

0.342

AC:

22102

AN:

64656

European-Finnish (FIN)

AF:

0.346

AC:

10491

AN:

30318

Middle Eastern (MID)

AF:

0.252

AC:

1285

AN:

5096

European-Non Finnish (NFE)

AF:

0.302

AC:

296857

AN:

983234

Other (OTH)

AF:

0.280

AC:

14484

AN:

51818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10510

21020

31531

42041

52551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10478

20956

31434

41912

52390

<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:

0.254

AC:

38305

AN:

150524

Hom.:

5849

Cov.:

AF XY:

0.256

AC XY:

18827

AN XY:

73460

show subpopulations

African (AFR)

AF:

0.0964

AC:

3960

AN:

41092

American (AMR)

AF:

0.242

AC:

3683

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1274

AN:

3460

East Asian (EAS)

AF:

0.0533

AC:

265

AN:

4968

South Asian (SAS)

AF:

0.366

AC:

1745

AN:

4762

European-Finnish (FIN)

AF:

0.391

AC:

4059

AN:

10382

Middle Eastern (MID)

AF:

0.234

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.330

AC:

22205

AN:

67370

Other (OTH)

AF:

0.256

AC:

538

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1356

2712

4068

5424

6780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.265

Hom.:

675

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

May 14, 2016

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 19, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital cerebellar hypoplasia

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

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

PhyloP100

2.2

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over