9-2621482-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000453601.5(VLDLR-AS1):n.274+618G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
VLDLR-AS1
ENST00000453601.5 intron
ENST00000453601.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0700
Publications
8 publications found
Genes affected
VLDLR-AS1 (HGNC:49621): (VLDLR antisense RNA 1)
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 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
- cerebellar ataxia, intellectual disability, and dysequilibriumInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000453601.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| VLDLR-AS1 | NR_015375.2 | n.274+618G>A | intron | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| VLDLR-AS1 | ENST00000453601.5 | TSL:1 | n.274+618G>A | intron | N/A | ||||
| VLDLR | ENST00000382096.6 | TSL:5 | c.-71+179C>T | intron | N/A | ENSP00000371528.2 | Q5VVF8 | ||
| VLDLR-AS1 | ENST00000657742.1 | n.274+618G>A | intron | N/A |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151982Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151982
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000405 AC: 1AN: 246780Hom.: 0 AF XY: 0.00000797 AC XY: 1AN XY: 125394 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
246780
Hom.:
AF XY:
AC XY:
1
AN XY:
125394
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
7022
American (AMR)
AF:
AC:
0
AN:
7352
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
9158
East Asian (EAS)
AF:
AC:
0
AN:
22836
South Asian (SAS)
AF:
AC:
0
AN:
2592
European-Finnish (FIN)
AF:
AC:
0
AN:
20686
Middle Eastern (MID)
AF:
AC:
0
AN:
1306
European-Non Finnish (NFE)
AF:
AC:
1
AN:
159464
Other (OTH)
AF:
AC:
0
AN:
16364
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 0.00000658 AC: 1AN: 151982Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74220 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151982
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74220
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41372
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5154
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67980
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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