rs2239317

Variant names:

• chr16-3870739-C-G
• rs2239317
• NM_004380.3:c.85+9093G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3870739-C-G
• chr16-3870739-C-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 6 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: 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.85+9093G>C		intron_variant	Intron 1 of 30	ENST00000262367.10	NP_004371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREBBP	ENST00000262367.10	c.85+9093G>C		intron_variant	Intron 1 of 30	1	NM_004380.3	ENSP00000262367.5
CREBBP	ENST00000382070.7	c.85+9093G>C		intron_variant	Intron 1 of 29	1		ENSP00000371502.3

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11878 AN: 152134 Hom.: 675 Cov.: 31

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

African (AFR) AF: 0.0178 AC: 741 AN: 41556

American (AMR) AF: 0.0627 AC: 959 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0799 AC: 277 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1502 AN: 5176

South Asian (SAS) AF: 0.101 AC: 486 AN: 4830

European-Finnish (FIN) AF: 0.0982 AC: 1041 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0963 AC: 6550 AN: 68016

Other (OTH) AF: 0.100 AC: 211 AN: 2106

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
PhyloP100		1.2
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: rs2239317; hg19: chr16-3920740;