rs201047390

Variant names:

• chr16-3727692-A-AG
• rs201047390
• NM_004380.3:c.*25dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004380.3(CREBBP):​c.*25dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,612,360 control chromosomes in the GnomAD database, including 290 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (23 hom., cov: 31)
  • Exomes 𝑓: 0.012 (267 hom.)
• Consequence: CREBBP NM_004380.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51
• Publications: 2 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 -10 ACMG points.

• BP6: Variant 16-3727692-A-AG is Benign according to our data. Variant chr16-3727692-A-AG is described in ClinVar as [Benign]. Clinvar id is 1268812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.*25dupC		3_prime_UTR_variant	Exon 31 of 31	ENST00000262367.10	NP_004371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREBBP	ENST00000262367.10	c.*25dupC		3_prime_UTR_variant	Exon 31 of 31	1	NM_004380.3	ENSP00000262367.5
CREBBP	ENST00000382070.7	c.*25dupC		3_prime_UTR_variant	Exon 30 of 30	1		ENSP00000371502.3

Frequencies

GnomAD3 genomes AF: 0.00827 AC: 1244 AN: 150498 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00843

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00728

Gnomad OTH AF: 0.0130

GnomAD2 exomes AF: 0.0147 AC: 3686 AN: 250384 AF XY: 0.0172

Gnomad AFR exome AF: 0.00162

Gnomad AMR exome AF: 0.00504

Gnomad ASJ exome AF: 0.0471

Gnomad EAS exome AF: 0.0191

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00833

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0119 AC: 17397 AN: 1461748 Hom.: 267 Cov.: 32 AF XY: 0.0133 AC XY: 9694 AN XY: 727184

African (AFR) AF: 0.00188 AC: 63 AN: 33478

American (AMR) AF: 0.00541 AC: 242 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0466 AC: 1219 AN: 26136

East Asian (EAS) AF: 0.0235 AC: 933 AN: 39700

South Asian (SAS) AF: 0.0521 AC: 4496 AN: 86258

European-Finnish (FIN) AF: 0.00186 AC: 99 AN: 53282

Middle Eastern (MID) AF: 0.0316 AC: 182 AN: 5768

European-Non Finnish (NFE) AF: 0.00831 AC: 9238 AN: 1112008

Other (OTH) AF: 0.0153 AC: 925 AN: 60396

GnomAD4 genome AF: 0.00826 AC: 1244 AN: 150612 Hom.: 23 Cov.: 31 AF XY: 0.00879 AC XY: 648 AN XY: 73690

African (AFR) AF: 0.00177 AC: 71 AN: 40020

American (AMR) AF: 0.00842 AC: 128 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3470

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5178

South Asian (SAS) AF: 0.0549 AC: 265 AN: 4824

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00728 AC: 495 AN: 67996

Other (OTH) AF: 0.0129 AC: 27 AN: 2098

Alfa AF: 0.0119 Hom.: 3

Bravo AF: 0.00755

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
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: rs201047390; hg19: chr16-3777693;