chr16-3770722-T-C
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_004380.3(CREBBP):c.2728A>G(p.Thr910Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,613,886 control chromosomes in the GnomAD database, including 9 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T910S) has been classified as Likely benign.
Frequency
Consequence
NM_004380.3 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 |
---|---|---|---|---|---|---|---|
CREBBP | NM_004380.3 | c.2728A>G | p.Thr910Ala | missense_variant | 14/31 | ENST00000262367.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CREBBP | ENST00000262367.10 | c.2728A>G | p.Thr910Ala | missense_variant | 14/31 | 1 | NM_004380.3 | P1 | |
CREBBP | ENST00000382070.7 | c.2614A>G | p.Thr872Ala | missense_variant | 13/30 | 1 | |||
CREBBP | ENST00000570939.2 | c.1333A>G | p.Thr445Ala | missense_variant | 9/23 | 5 | |||
CREBBP | ENST00000573672.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00232 AC: 353AN: 151926Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00240 AC: 603AN: 251324Hom.: 2 AF XY: 0.00226 AC XY: 307AN XY: 135840
GnomAD4 exome AF: 0.00239 AC: 3487AN: 1461844Hom.: 9 Cov.: 33 AF XY: 0.00239 AC XY: 1739AN XY: 727218
GnomAD4 genome ? AF: 0.00232 AC: 353AN: 152042Hom.: 0 Cov.: 31 AF XY: 0.00268 AC XY: 199AN XY: 74324
ClinVar
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2019 | This variant is associated with the following publications: (PMID: 20684013) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | CREBBP: BP4, BS1 - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 01, 2016 | - - |
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, University Medical Center Utrecht | - | - - |
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 18, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 15, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Tip-toe gait Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino | Apr 04, 2022 | - - |
Rubinstein-Taybi syndrome due to CREBBP mutations Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2010 | - - |
CREBBP-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 15, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Rubinstein-Taybi syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Intellectual disability Benign:1
Likely benign, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at