rs199821421
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004380.3(CREBBP):c.6324C>T(p.Tyr2108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
CREBBP
NM_004380.3 synonymous
NM_004380.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.215
Genes affected
CREBBP (HGNC:2348): (CREB binding protein) This gene is ubiquitously expressed and is involved in the transcriptional coactivation of many different transcription factors. First isolated as a nuclear protein that binds to cAMP-response element binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. The protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex. This protein acetylates both histone and non-histone proteins. This protein shares regions of very high sequence similarity with protein p300 in its bromodomain, cysteine-histidine-rich regions, and histone acetyltransferase domain. Mutations in this gene cause Rubinstein-Taybi syndrome (RTS). Chromosomal translocations involving this gene have been associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 16-3728723-G-A is Benign according to our data. Variant chr16-3728723-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 767625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.215 with no splicing effect.
BS2
?
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CREBBP | NM_004380.3 | c.6324C>T | p.Tyr2108= | synonymous_variant | 31/31 | ENST00000262367.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CREBBP | ENST00000262367.10 | c.6324C>T | p.Tyr2108= | synonymous_variant | 31/31 | 1 | NM_004380.3 | P1 | |
CREBBP | ENST00000382070.7 | c.6210C>T | p.Tyr2070= | synonymous_variant | 30/30 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000520 AC: 13AN: 249994Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135202
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461602Hom.: 0 Cov.: 33 AF XY: 0.0000385 AC XY: 28AN XY: 727122
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GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CREBBP-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 09, 2023 | 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). - |
Rubinstein-Taybi syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at