rs17136507

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004380.3(CREBBP):​c.3780-861A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,128 control chromosomes in the GnomAD database, including 2,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2721 hom., cov: 32)

Consequence

CREBBP
NM_004380.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309

Publications

7 publications found
Variant links:
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]
CREBBP Gene-Disease associations (from GenCC):
  • Rubinstein-Taybi syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
  • Rubinstein-Taybi syndrome due to CREBBP mutations
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • Menke-Hennekam syndrome 1
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CREBBPNM_004380.3 linkc.3780-861A>G intron_variant Intron 20 of 30 ENST00000262367.10 NP_004371.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CREBBPENST00000262367.10 linkc.3780-861A>G intron_variant Intron 20 of 30 1 NM_004380.3 ENSP00000262367.5 Q92793-1
CREBBPENST00000382070.7 linkc.3666-861A>G intron_variant Intron 19 of 29 1 ENSP00000371502.3 Q92793-2
CREBBPENST00000570939.2 linkc.2415-861A>G intron_variant Intron 15 of 22 5 ENSP00000461002.2 I3L466
CREBBPENST00000573517.6 linkc.84-861A>G intron_variant Intron 2 of 6 5 ENSP00000460474.2 I3L3I5

Frequencies

GnomAD3 genomes
AF:
0.163
AC:
24760
AN:
152010
Hom.:
2720
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.303
Gnomad AMI
AF:
0.120
Gnomad AMR
AF:
0.203
Gnomad ASJ
AF:
0.134
Gnomad EAS
AF:
0.0501
Gnomad SAS
AF:
0.164
Gnomad FIN
AF:
0.117
Gnomad MID
AF:
0.180
Gnomad NFE
AF:
0.0868
Gnomad OTH
AF:
0.151
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.163
AC:
24791
AN:
152128
Hom.:
2721
Cov.:
32
AF XY:
0.165
AC XY:
12296
AN XY:
74364
show subpopulations
African (AFR)
AF:
0.302
AC:
12543
AN:
41468
American (AMR)
AF:
0.203
AC:
3109
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.134
AC:
466
AN:
3472
East Asian (EAS)
AF:
0.0504
AC:
261
AN:
5180
South Asian (SAS)
AF:
0.165
AC:
798
AN:
4824
European-Finnish (FIN)
AF:
0.117
AC:
1234
AN:
10588
Middle Eastern (MID)
AF:
0.180
AC:
53
AN:
294
European-Non Finnish (NFE)
AF:
0.0868
AC:
5904
AN:
68002
Other (OTH)
AF:
0.149
AC:
314
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1004
2009
3013
4018
5022
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
254
508
762
1016
1270
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.113
Hom.:
2457
Bravo
AF:
0.172
Asia WGS
AF:
0.131
AC:
456
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
1.0
DANN
Benign
0.46
PhyloP100
-0.31
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17136507; hg19: chr16-3800545; API