rs556442
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002335.4(LRP5):c.3357G>A(p.Val1119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,612,708 control chromosomes in the GnomAD database, including 366,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.57 ( 28392 hom., cov: 32)
Exomes 𝑓: 0.67 ( 337608 hom. )
Consequence
LRP5
NM_002335.4 synonymous
NM_002335.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.318
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 11-68425222-G-A is Benign according to our data. Variant chr11-68425222-G-A is described in ClinVar as [Benign]. Clinvar id is 258638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68425222-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.318 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP5 | NM_002335.4 | c.3357G>A | p.Val1119= | synonymous_variant | 15/23 | ENST00000294304.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP5 | ENST00000294304.12 | c.3357G>A | p.Val1119= | synonymous_variant | 15/23 | 1 | NM_002335.4 | P1 | |
LRP5 | ENST00000529993.5 | c.*1963G>A | 3_prime_UTR_variant, NMD_transcript_variant | 15/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.570 AC: 86698AN: 152010Hom.: 28386 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
86698
AN:
152010
Hom.:
Cov.:
32
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:
GnomAD3 exomes AF: 0.682 AC: 170521AN: 250022Hom.: 60581 AF XY: 0.695 AC XY: 94036AN XY: 135358
GnomAD3 exomes
AF:
AC:
170521
AN:
250022
Hom.:
AF XY:
AC XY:
94036
AN XY:
135358
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.674 AC: 984899AN: 1460580Hom.: 337608 Cov.: 62 AF XY: 0.679 AC XY: 493444AN XY: 726700
GnomAD4 exome
AF:
AC:
984899
AN:
1460580
Hom.:
Cov.:
62
AF XY:
AC XY:
493444
AN XY:
726700
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.570 AC: 86715AN: 152128Hom.: 28392 Cov.: 32 AF XY: 0.584 AC XY: 43445AN XY: 74380
GnomAD4 genome
?
AF:
AC:
86715
AN:
152128
Hom.:
Cov.:
32
AF XY:
AC XY:
43445
AN XY:
74380
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2407
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at