rs130008
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004380.3(CREBBP):c.4729-14G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,614,196 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 18 hom., cov: 32)
Exomes 𝑓: 0.018 ( 313 hom. )
Consequence
CREBBP
NM_004380.3 splice_polypyrimidine_tract, intron
NM_004380.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.509
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 16-3731951-C-G is Benign according to our data. Variant chr16-3731951-C-G is described in ClinVar as [Benign]. Clinvar id is 158381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1778/152334) while in subpopulation NFE AF= 0.0197 (1343/68022). AF 95% confidence interval is 0.0189. There are 18 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1778 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CREBBP | NM_004380.3 | c.4729-14G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000262367.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CREBBP | ENST00000262367.10 | c.4729-14G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004380.3 | P1 | |||
CREBBP | ENST00000382070.7 | c.4615-14G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
CREBBP | ENST00000571763.5 | n.519-14G>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 | |||||
CREBBP | ENST00000576720.1 | n.3552-14G>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0117 AC: 1778AN: 152216Hom.: 18 Cov.: 32
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GnomAD3 exomes AF: 0.0110 AC: 2731AN: 249022Hom.: 18 AF XY: 0.0110 AC XY: 1488AN XY: 134806
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GnomAD4 exome AF: 0.0184 AC: 26873AN: 1461862Hom.: 313 Cov.: 33 AF XY: 0.0177 AC XY: 12862AN XY: 727232
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GnomAD4 genome ? AF: 0.0117 AC: 1778AN: 152334Hom.: 18 Cov.: 32 AF XY: 0.0113 AC XY: 842AN XY: 74490
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 17, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Rubinstein-Taybi syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at