Variant rs130002 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.2113+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,501,598 control chromosomes in the GnomAD database, including 2,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 302 hom., cov: 32)

Exomes 𝑓: 0.021 ( 1850 hom. )

Consequence

CREBBP
NM_004380.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.61

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=-0.88).

BP6

Variant 16-3777930-T-C is Benign according to our data. Variant chr16-3777930-T-C is described in ClinVar as [Benign]. Clinvar id is 1249895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 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.2113+81A>G		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.2113+81A>G		intron_variant		1	NM_004380.3	ENSP00000262367	P1	Q92793-1

Frequencies

GnomAD3 genomes

AF:

0.0390

AC:

5941

AN:

152170

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0783

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00417

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0208

AC:

28065

AN:

1349310

Hom.:

1850

Cov.:

AF XY:

0.0243

AC XY:

16472

AN XY:

677360

show subpopulations

Gnomad4 AFR exome

AF:

0.0843

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.00985

Gnomad4 NFE exome

AF:

0.00301

Gnomad4 OTH exome

AF:

0.0328

GnomAD4 genome

AF:

0.0391

AC:

5953

AN:

152288

Hom.:

302

Cov.:

AF XY:

0.0422

AC XY:

3140

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0785

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.00417

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0308

Hom.:

Bravo

AF:

0.0406

Asia WGS

AF:

0.165

AC:

573

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.20

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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