rs11644593

Variant names:

• chr16-3821285-G-A
• rs11644593
• NM_004380.3:c.799-10506C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3821285-G-A
• chr16-3821285-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004380.3(CREBBP):​c.799-10506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,288 control chromosomes in the GnomAD database, including 621 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 0.076 (621 hom., cov: 32)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 9 publications found

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: Illumina, ClinGen
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004380.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBBP	NM_004380.3	MANE Select	c.799-10506C>T		intron	N/A	NP_004371.2	Q92793-1
	CREBBP	NM_001079846.1		c.799-10506C>T		intron	N/A	NP_001073315.1	Q92793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBBP	ENST00000262367.10	TSL:1 MANE Select	c.799-10506C>T		intron	N/A	ENSP00000262367.5	Q92793-1
	CREBBP	ENST00000382070.7	TSL:1	c.799-10506C>T		intron	N/A	ENSP00000371502.3	Q92793-2
	CREBBP	ENST00000636895.1	TSL:5	n.26-8213C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11546 AN: 152170 Hom.: 619 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0967

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0933

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0759 AC: 11553 AN: 152288 Hom.: 621 Cov.: 32 AF XY: 0.0778 AC XY: 5791 AN XY: 74460

African (AFR) AF: 0.0171 AC: 710 AN: 41564

American (AMR) AF: 0.0583 AC: 893 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0967 AC: 335 AN: 3466

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5172

South Asian (SAS) AF: 0.101 AC: 488 AN: 4828

European-Finnish (FIN) AF: 0.0916 AC: 972 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0942 AC: 6407 AN: 68020

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0667 Hom.: 178

Bravo AF: 0.0725

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.58
PhyloP100		-0.091
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

Other links and lift over

dbSNP: rs11644593; hg19: chr16-3871286;