Variant rs129967 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.192

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
CREBBP	NM_004380.3 linkuse as main transcript	c.4280+42C>T		intron_variant		ENST00000262367.10	NP_004371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREBBP	ENST00000262367.10 linkuse as main transcript	c.4280+42C>T		intron_variant		1	NM_004380.3	ENSP00000262367	P1	Q92793-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22038

AN:

152006

Hom.:

4113

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0388

AC XY:

28225

AN XY:

726724

show subpopulations

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.:

AF XY:

0.142

AC XY:

10584

AN XY:

74378

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over