chr11-68446521-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_002335.4(LRP5):c.4574C>T(p.Ala1525Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,754 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1525A) has been classified as Likely benign.
Frequency
Consequence
NM_002335.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP5 | NM_002335.4 | c.4574C>T | p.Ala1525Val | missense_variant | 22/23 | ENST00000294304.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP5 | ENST00000294304.12 | c.4574C>T | p.Ala1525Val | missense_variant | 22/23 | 1 | NM_002335.4 | P1 | |
LRP5 | ENST00000529993.5 | c.*3180C>T | 3_prime_UTR_variant, NMD_transcript_variant | 22/23 | 1 | ||||
LRP5 | ENST00000529702.1 | c.245C>T | p.Ala82Val | missense_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00959 AC: 1460AN: 152214Hom.: 11 Cov.: 32
GnomAD3 exomes AF: 0.00770 AC: 1934AN: 251260Hom.: 13 AF XY: 0.00746 AC XY: 1013AN XY: 135870
GnomAD4 exome AF: 0.0107 AC: 15642AN: 1461422Hom.: 110 Cov.: 31 AF XY: 0.0103 AC XY: 7482AN XY: 727050
GnomAD4 genome ? AF: 0.00958 AC: 1460AN: 152332Hom.: 11 Cov.: 32 AF XY: 0.00881 AC XY: 656AN XY: 74480
ClinVar
Submissions by phenotype
not provided Benign:8
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | LRP5: BP4, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 18, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 16956801) - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2014 | - - |
Osteogenesis imperfecta Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 18, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at