11-68312732-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_002335.4(LRP5):c.18C>T(p.Pro6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,052,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000066 ( 0 hom. )
Consequence
LRP5
NM_002335.4 synonymous
NM_002335.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.350
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 11-68312732-C-T is Benign according to our data. Variant chr11-68312732-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1908724.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.35 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRP5 | NM_002335.4 | c.18C>T | p.Pro6= | synonymous_variant | 1/23 | ENST00000294304.12 | NP_002326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP5 | ENST00000294304.12 | c.18C>T | p.Pro6= | synonymous_variant | 1/23 | 1 | NM_002335.4 | ENSP00000294304 | P1 | |
LRP5 | ENST00000529993.5 | c.18C>T | p.Pro6= | synonymous_variant, NMD_transcript_variant | 1/23 | 1 | ENSP00000436652 |
Frequencies
GnomAD3 genomes AF: 0.0000139 AC: 2AN: 144102Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000660 AC: 6AN: 908416Hom.: 0 Cov.: 28 AF XY: 0.00000924 AC XY: 4AN XY: 432806
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GnomAD4 genome AF: 0.0000139 AC: 2AN: 144102Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 70118
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
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Benign
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at