rs2277268
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002335.4(LRP5):c.1932G>A(p.Glu644Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 1,614,058 control chromosomes in the GnomAD database, including 3,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.063 ( 358 hom., cov: 33)
Exomes 𝑓: 0.068 ( 3518 hom. )
Consequence
LRP5
NM_002335.4 synonymous
NM_002335.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.629
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 11-68406654-G-A is Benign according to our data. Variant chr11-68406654-G-A is described in ClinVar as [Benign]. Clinvar id is 258635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68406654-G-A is described in Lovd as [Likely_pathogenic]. Variant chr11-68406654-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.629 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRP5 | NM_002335.4 | c.1932G>A | p.Glu644Glu | synonymous_variant | 9/23 | ENST00000294304.12 | NP_002326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP5 | ENST00000294304.12 | c.1932G>A | p.Glu644Glu | synonymous_variant | 9/23 | 1 | NM_002335.4 | ENSP00000294304.6 | ||
LRP5 | ENST00000529993.5 | n.*538G>A | non_coding_transcript_exon_variant | 9/23 | 1 | ENSP00000436652.1 | ||||
LRP5 | ENST00000529993.5 | n.*538G>A | 3_prime_UTR_variant | 9/23 | 1 | ENSP00000436652.1 |
Frequencies
GnomAD3 genomes AF: 0.0630 AC: 9590AN: 152118Hom.: 357 Cov.: 33
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GnomAD3 exomes AF: 0.0583 AC: 14656AN: 251324Hom.: 465 AF XY: 0.0585 AC XY: 7954AN XY: 135888
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GnomAD4 exome AF: 0.0675 AC: 98731AN: 1461822Hom.: 3518 Cov.: 33 AF XY: 0.0667 AC XY: 48481AN XY: 727206
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GnomAD4 genome AF: 0.0631 AC: 9600AN: 152236Hom.: 358 Cov.: 33 AF XY: 0.0615 AC XY: 4579AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at