rs17136507

chr16-3750544-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CREBBP	NM_004380.3	c.3780-861A>G		intron_variant		ENST00000262367.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREBBP	ENST00000262367.10	c.3780-861A>G		intron_variant		1	NM_004380.3	P1
CREBBP	ENST00000382070.7	c.3666-861A>G		intron_variant		1
CREBBP	ENST00000570939.2	c.2415-861A>G		intron_variant		5
CREBBP	ENST00000573517.6	c.86-861A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24760 AN: 152010 Hom.: 2720 Cov.: 32

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

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0504

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0868

Gnomad4 OTH AF: 0.149

Alfa AF: 0.105 Hom.: 1485

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

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

Other links and lift over

dbSNP: rs17136507; hg19: chr16-3800545;