chr16-3761555-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004380.3(CREBBP):​c.3251-2583T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000772 in 518,056 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CREBBP
NM_004380.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.187

Publications

24 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: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CREBBPNM_004380.3 linkc.3251-2583T>G intron_variant Intron 16 of 30 ENST00000262367.10 NP_004371.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CREBBPENST00000262367.10 linkc.3251-2583T>G intron_variant Intron 16 of 30 1 NM_004380.3 ENSP00000262367.5 Q92793-1
CREBBPENST00000382070.7 linkc.3137-2583T>G intron_variant Intron 15 of 29 1 ENSP00000371502.3 Q92793-2
CREBBPENST00000570939.2 linkc.1856-2583T>G intron_variant Intron 11 of 22 5 ENSP00000461002.2 I3L466

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151748
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000879
AC:
2
AN:
227576
AF XY:
0.00000795
show subpopulations
Gnomad AFR exome
AF:
0.000145
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000546
AC:
2
AN:
366308
Hom.:
0
Cov.:
0
AF XY:
0.00000952
AC XY:
2
AN XY:
210058
show subpopulations
African (AFR)
AF:
0.000191
AC:
2
AN:
10484
American (AMR)
AF:
0.00
AC:
0
AN:
36260
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
11730
East Asian (EAS)
AF:
0.00
AC:
0
AN:
13122
South Asian (SAS)
AF:
0.00
AC:
0
AN:
66732
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
16880
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2852
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
191656
Other (OTH)
AF:
0.00
AC:
0
AN:
16592
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151748
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74082
show subpopulations
African (AFR)
AF:
0.0000484
AC:
2
AN:
41300
American (AMR)
AF:
0.00
AC:
0
AN:
15252
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5142
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4776
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10570
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67930
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
44894

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.2
DANN
Benign
0.47
PhyloP100
-0.19

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: rs886528; hg19: chr16-3811556; API