rs130018
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004380.3(CREBBP):c.1676+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,603,678 control chromosomes in the GnomAD database, including 2,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.075 ( 1152 hom., cov: 32)
Exomes 𝑓: 0.017 ( 1208 hom. )
Consequence
CREBBP
NM_004380.3 intron
NM_004380.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.497
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=-0.87).
BP6
?
Variant 16-3781186-T-A is Benign according to our data. Variant chr16-3781186-T-A is described in ClinVar as [Benign]. Clinvar id is 95028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CREBBP | NM_004380.3 | c.1676+18A>T | intron_variant | ENST00000262367.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CREBBP | ENST00000262367.10 | c.1676+18A>T | intron_variant | 1 | NM_004380.3 | P1 | |||
CREBBP | ENST00000382070.7 | c.1562+18A>T | intron_variant | 1 | |||||
CREBBP | ENST00000570939.2 | c.281+18A>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0749 AC: 11386AN: 152084Hom.: 1144 Cov.: 32
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GnomAD3 exomes AF: 0.0288 AC: 7232AN: 251126Hom.: 534 AF XY: 0.0244 AC XY: 3317AN XY: 135714
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GnomAD4 exome AF: 0.0173 AC: 25088AN: 1451476Hom.: 1208 Cov.: 29 AF XY: 0.0166 AC XY: 11981AN XY: 722788
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GnomAD4 genome ? AF: 0.0751 AC: 11437AN: 152202Hom.: 1152 Cov.: 32 AF XY: 0.0713 AC XY: 5307AN XY: 74422
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 18, 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
Benign
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