rs9392

Positions:

• chr16-3725168-G-A
• chr16-3725168-G-C
• chr16-3725168-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004380.3(CREBBP):​c.*2550C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 233,296 control chromosomes in the GnomAD database, including 6,831 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 0.22 (3894 hom., cov: 33)
  • Exomes 𝑓: 0.25 (2937 hom.)
• Consequence: CREBBP NM_004380.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREBBP	NM_004380.3	c.*2550C>T		3_prime_UTR_variant	31/31	ENST00000262367.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREBBP	ENST00000262367.10	c.*2550C>T		3_prime_UTR_variant	31/31	1	NM_004380.3	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33458 AN: 152038 Hom.: 3894 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.252 AC: 20433 AN: 81140 Hom.: 2937 Cov.: 0 AF XY: 0.255 AC XY: 9527 AN XY: 37352

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.220 AC: 33465 AN: 152156 Hom.: 3894 Cov.: 33 AF XY: 0.222 AC XY: 16523 AN XY: 74392

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.220

Alfa AF: 0.221 Hom.: 978

Bravo AF: 0.210

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.85

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: rs9392; hg19: chr16-3775169;