rs129967

chr16-3739536-G-Achr16-3739536-G-Cchr16-3739536-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004380.3(CREBBP):c.4280+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,612,982 control chromosomes in the GnomAD database, including 9,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (4131 hom., cov: 33)
  • Exomes 𝑓: 0.038 (5454 hom.)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.192

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 16-3739536-G-A is Benign according to our data. Variant chr16-3739536-G-A is described in ClinVar as [Benign]. Clinvar id is 1242603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREBBP	NM_004380.3	c.4280+42C>T		intron_variant		ENST00000262367.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREBBP	ENST00000262367.10	c.4280+42C>T		intron_variant		1	NM_004380.3	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22038 AN: 152006 Hom.: 4113 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.0759 AC: 19019 AN: 250528 Hom.: 2373 AF XY: 0.0711 AC XY: 9629 AN XY: 135470

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0752

Gnomad EAS exome AF: 0.220

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.0513

GnomAD4 exome AF: 0.0376 AC: 54889 AN: 1460858 Hom.: 5454 Cov.: 31 AF XY: 0.0388 AC XY: 28225 AN XY: 726724

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.0417

Gnomad4 ASJ exome AF: 0.0780

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.00414

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.0685

GnomAD4 genome AF: 0.145 AC: 22100 AN: 152124 Hom.: 4131 Cov.: 33 AF XY: 0.142 AC XY: 10584 AN XY: 74378

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.0727

Gnomad4 ASJ AF: 0.0850

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.00340

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0490 Hom.: 1028

Bravo AF: 0.165

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.3
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs129967; hg19: chr16-3789537; COSMIC: COSV52117696; COSMIC: COSV52117696;