chr11-68357679-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP3BS1
The NM_001291902.2(LRP5):c.-1248C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,614,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001291902.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP5 | ENST00000294304.12 | c.518C>T | p.Thr173Met | missense_variant | Exon 3 of 23 | 1 | NM_002335.4 | ENSP00000294304.6 | ||
LRP5 | ENST00000529993.5 | n.518C>T | non_coding_transcript_exon_variant | Exon 3 of 23 | 1 | ENSP00000436652.1 |
Frequencies
GnomAD3 genomes AF: 0.000526 AC: 80AN: 152228Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000391 AC: 98AN: 250806Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135660
GnomAD4 exome AF: 0.000225 AC: 329AN: 1461754Hom.: 0 Cov.: 32 AF XY: 0.000224 AC XY: 163AN XY: 727148
GnomAD4 genome AF: 0.000525 AC: 80AN: 152346Hom.: 1 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74494
ClinVar
Submissions by phenotype
not provided Benign:2
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Reported previously in association with familial exudative vitreoretinopathy, but the variant was inherited from an unaffected parent (Toomes et al., 2004; Li et al., 2018); Published functional studies demonstrate no damaging effect (Ai et al., 2005); This variant is associated with the following publications: (PMID: 22995991, 15923613, 16252235, 26348019, 15024691, 20340138, 24715757, 30452590) -
LRP5-related disorder Uncertain:1
The LRP5 c.518C>T variant is predicted to result in the amino acid substitution p.Thr173Met. This variant has been reported in two individuals with familial exudative vitreoretinopathy (Toomes et al. 2004. PubMed ID: 15024691; Li et al. 2018. PubMed ID: 30452590), and in an individual with high bone mass (Gregson et al. 2015. PubMed ID: 26348019). However, this variant is reported in 0.15% of alleles in individuals of East Asian descent in gnomAD, including 1 homozygous individual in the newest dataset (https://gnomad.broadinstitute.org/variant/11-68357679-C-T?dataset=gnomad_r4). Therefore, although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at