rs1302427305
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004380.3(CREBBP):c.1237C>T(p.Arg413*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004380.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CREBBP | NM_004380.3 | c.1237C>T | p.Arg413* | stop_gained | Exon 5 of 31 | ENST00000262367.10 | NP_004371.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rubinstein-Taybi syndrome due to CREBBP mutations Pathogenic:4
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This CREBBP variant (rs1302427305) is absent from a large population dataset and has been reported in ClinVar. It has been reported in unrelated individuals with RSTS1. This nonsense variant results in a premature termination codon in exon 5 likely leading to nonsense-mediated decay and lack of protein production. We consider c.1237C>T to be pathogenic. -
not provided Pathogenic:1
The R413X nonsense variant in the CREBBP gene has been reported previously in association with Rubinstein-Taybi syndrome (Coupry et al., 2002; Schorry et al., 2008). The R413X variant was not observed in approximately 6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at