rs2239317

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004380.3(CREBBP):​c.85+9093G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 152,252 control chromosomes in the GnomAD database, including 678 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 0.078 ( 678 hom., cov: 31)

Consequence

CREBBP
NM_004380.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CREBBPNM_004380.3 linkuse as main transcriptc.85+9093G>C intron_variant ENST00000262367.10 NP_004371.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CREBBPENST00000262367.10 linkuse as main transcriptc.85+9093G>C intron_variant 1 NM_004380.3 ENSP00000262367.5 Q92793-1
CREBBPENST00000382070.7 linkuse as main transcriptc.85+9093G>C intron_variant 1 ENSP00000371502.3 Q92793-2

Frequencies

GnomAD3 genomes
AF:
0.0781
AC:
11878
AN:
152134
Hom.:
675
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0179
Gnomad AMI
AF:
0.0945
Gnomad AMR
AF:
0.0628
Gnomad ASJ
AF:
0.0799
Gnomad EAS
AF:
0.290
Gnomad SAS
AF:
0.100
Gnomad FIN
AF:
0.0982
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.0963
Gnomad OTH
AF:
0.0960
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0781
AC:
11886
AN:
152252
Hom.:
678
Cov.:
31
AF XY:
0.0804
AC XY:
5986
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0178
Gnomad4 AMR
AF:
0.0627
Gnomad4 ASJ
AF:
0.0799
Gnomad4 EAS
AF:
0.290
Gnomad4 SAS
AF:
0.101
Gnomad4 FIN
AF:
0.0982
Gnomad4 NFE
AF:
0.0963
Gnomad4 OTH
AF:
0.100
Alfa
AF:
0.0389
Hom.:
28
Bravo
AF:
0.0744
Asia WGS
AF:
0.159
AC:
552
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
7.8
DANN
Benign
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2239317; hg19: chr16-3920740; API