rs72555376
Your query was ambiguous. Multiple possible variants found:
- chr11-68312746-CGCTGCTGCTGCTGCT-C
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_002335.4(LRP5):c.46_60delCTGCTGCTGCTGCTG(p.Leu16_Leu20del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,061,244 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000069 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000033 ( 0 hom. )
Consequence
LRP5
NM_002335.4 conservative_inframe_deletion
NM_002335.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.307
Publications
4 publications found
Genes affected
LRP5 (HGNC:6697): (LDL receptor related protein 5) This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
LRP5 Gene-Disease associations (from GenCC):
- bone mineral density quantitative trait locus 1Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- exudative vitreoretinopathy 4Inheritance: AD, SD, Unknown Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
- inherited retinal dystrophyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- osteoporosis-pseudoglioma syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- autosomal dominant osteosclerosis, Worth typeInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- polycystic liver disease 4 with or without kidney cystsInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- autosomal dominant osteopetrosis 1Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
- exudative vitreoretinopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hyperostosis corticalis generalisataInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteosclerosis-developmental delay-craniosynostosis syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- polycystic liver disease 1Inheritance: AD 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.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002335.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| LRP5 | NM_002335.4 | MANE Select | c.46_60delCTGCTGCTGCTGCTG | p.Leu16_Leu20del | conservative_inframe_deletion | Exon 1 of 23 | NP_002326.2 | ||
| LRP5 | NM_001291902.2 | c.-1720_-1706delCTGCTGCTGCTGCTG | 5_prime_UTR | Exon 1 of 23 | NP_001278831.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LRP5 | ENST00000294304.12 | TSL:1 MANE Select | c.46_60delCTGCTGCTGCTGCTG | p.Leu16_Leu20del | conservative_inframe_deletion | Exon 1 of 23 | ENSP00000294304.6 | ||
| LRP5 | ENST00000529993.5 | TSL:1 | n.46_60delCTGCTGCTGCTGCTG | non_coding_transcript_exon | Exon 1 of 23 | ENSP00000436652.1 | |||
| LRP5 | ENST00000909991.1 | c.46_60delCTGCTGCTGCTGCTG | p.Leu16_Leu20del | conservative_inframe_deletion | Exon 1 of 23 | ENSP00000580050.1 |
Frequencies
GnomAD3 genomes 0.00000693 AC: 1AN: 144332Hom.: 0 Cov.: 28 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
144332
Hom.:
Cov.:
28
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 AF: 0.00000327 AC: 3AN: 916912Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 438488 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
916912
Hom.:
AF XY:
AC XY:
0
AN XY:
438488
show subpopulations
African (AFR)
AF:
AC:
0
AN:
17012
American (AMR)
AF:
AC:
0
AN:
6652
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
8138
East Asian (EAS)
AF:
AC:
0
AN:
5840
South Asian (SAS)
AF:
AC:
0
AN:
28828
European-Finnish (FIN)
AF:
AC:
0
AN:
5870
Middle Eastern (MID)
AF:
AC:
0
AN:
1966
European-Non Finnish (NFE)
AF:
AC:
3
AN:
811342
Other (OTH)
AF:
AC:
0
AN:
31264
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
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
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>80
Age
GnomAD4 genome 0.00000693 AC: 1AN: 144332Hom.: 0 Cov.: 28 AF XY: 0.0000142 AC XY: 1AN XY: 70222 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
144332
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
70222
show subpopulations
African (AFR)
AF:
AC:
1
AN:
39912
American (AMR)
AF:
AC:
0
AN:
14634
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3366
East Asian (EAS)
AF:
AC:
0
AN:
4942
South Asian (SAS)
AF:
AC:
0
AN:
4750
European-Finnish (FIN)
AF:
AC:
0
AN:
8356
Middle Eastern (MID)
AF:
AC:
0
AN:
298
European-Non Finnish (NFE)
AF:
AC:
0
AN:
65194
Other (OTH)
AF:
AC:
0
AN:
1998
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
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.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
1
-
not provided (1)
-
1
-
Osteoporosis;C0432252:Osteoporosis with pseudoglioma;C0432273:Worth disease;C1843330:Autosomal dominant osteopetrosis 1;C1851402:Exudative vitreoretinopathy 1;C1866079:Bone mineral density quantitative trait locus 1;C1866176:Exudative vitreoretinopathy 4;C4693479:Polycystic liver disease 4 with or without kidney cysts (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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