rs115198029
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006371.5(CRTAP):c.1039C>T(p.Leu347Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,614,124 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006371.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.1039C>T | p.Leu347Phe | missense_variant | Exon 5 of 7 | ENST00000320954.11 | NP_006362.1 | |
CRTAP | NM_001393363.1 | c.1039C>T | p.Leu347Phe | missense_variant | Exon 5 of 6 | NP_001380292.1 | ||
CRTAP | NM_001393364.1 | c.910C>T | p.Leu304Phe | missense_variant | Exon 4 of 6 | NP_001380293.1 | ||
CRTAP | NM_001393365.1 | c.889C>T | p.Leu297Phe | missense_variant | Exon 4 of 6 | NP_001380294.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.1039C>T | p.Leu347Phe | missense_variant | Exon 5 of 7 | 1 | NM_006371.5 | ENSP00000323696.5 | ||
CRTAP | ENST00000449224.1 | c.910C>T | p.Leu304Phe | missense_variant | Exon 4 of 6 | 2 | ENSP00000409997.1 | |||
CRTAP | ENST00000485310.1 | n.*71C>T | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00247 AC: 376AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00201 AC: 506AN: 251494Hom.: 1 AF XY: 0.00200 AC XY: 272AN XY: 135920
GnomAD4 exome AF: 0.00312 AC: 4557AN: 1461812Hom.: 10 Cov.: 40 AF XY: 0.00303 AC XY: 2207AN XY: 727222
GnomAD4 genome AF: 0.00247 AC: 376AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.00207 AC XY: 154AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Reported in an individual with osteogenesis imperfecta who also has a pathogenic variant in the COL1A1 gene (PMID: 32169308); Identified in a patient with osteoporosis and relatives with osteopenia or osteoporosis (PMID: 35313637); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32169308, 35313637, 30389107, 33469725) -
CRTAP: BP4 -
BS1 -
Osteogenesis imperfecta type 7 Uncertain:2Benign:1
The CRTAP c.1039C>T; p.Leu347Phe variant (rs115198029), to our knowledge, is not reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 439559). This variant is found in the general population with an overall allele frequency of 0.20% (562/282,886 alleles, including a single homozygote) in the Genome Aggregation Database. The leucine at codon 347 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.354). Based on the available information, the clinical significance of this variant is uncertain. -
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
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Osteogenesis imperfecta Benign:1
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CRTAP-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at