rs130018

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004380.3(CREBBP):c.1676+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,603,678 control chromosomes in the GnomAD database, including 2,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 1152 hom., cov: 32)

Exomes 𝑓: 0.017 ( 1208 hom. )

Consequence

CREBBP
NM_004380.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.497

Publications

4 publications found

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 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)

CREBBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-3781186-T-A is Benign according to our data. Variant chr16-3781186-T-A is described in ClinVar as [Benign]. Clinvar id is 95028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREBBP	NM_004380.3 link	c.1676+18A>T		intron_variant	Intron 7 of 30	ENST00000262367.10	NP_004371.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CREBBP	ENST00000262367.10 link	c.1676+18A>T	intron_variant	Intron 7 of 30	1	NM_004380.3	ENSP00000262367.5	Q92793-1
CREBBP	ENST00000382070.7 link	c.1562+18A>T	intron_variant	Intron 6 of 29	1		ENSP00000371502.3	Q92793-2
CREBBP	ENST00000570939.2 link	c.281+18A>T	intron_variant	Intron 2 of 22	5		ENSP00000461002.2	I3L466

Frequencies

GnomAD3 genomes

AF:

0.0749

AC:

11386

AN:

152084

Hom.:

1144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0411

Gnomad ASJ

AF:

0.0665

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00944

Gnomad OTH

AF:

0.0722

GnomAD2 exomes

AF:

0.0288

AC:

7232

AN:

251126

AF XY:

0.0244

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.0192

Gnomad ASJ exome

AF:

0.0635

Gnomad EAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00988

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0173

AC:

25088

AN:

1451476

Hom.:

1208

Cov.:

AF XY:

0.0166

AC XY:

11981

AN XY:

722788

show subpopulations

African (AFR)

AF:

0.239

AC:

7932

AN:

33252

American (AMR)

AF:

0.0222

AC:

991

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0627

AC:

1634

AN:

26046

East Asian (EAS)

AF:

0.0236

AC:

937

AN:

39620

South Asian (SAS)

AF:

0.0133

AC:

1144

AN:

85962

European-Finnish (FIN)

AF:

0.00187

AC:

100

AN:

53406

Middle Eastern (MID)

AF:

0.0518

AC:

298

AN:

5748

European-Non Finnish (NFE)

AF:

0.00920

AC:

10149

AN:

1102666

Other (OTH)

AF:

0.0317

AC:

1903

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1082

2164

3246

4328

5410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0751

AC:

11437

AN:

152202

Hom.:

1152

Cov.:

AF XY:

0.0713

AC XY:

5307

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.232

AC:

9630

AN:

41462

American (AMR)

AF:

0.0410

AC:

628

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0665

AC:

231

AN:

3472

East Asian (EAS)

AF:

0.0133

AC:

AN:

5188

South Asian (SAS)

AF:

0.0129

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00944

AC:

642

AN:

68024

Other (OTH)

AF:

0.0715

AC:

151

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

470

940

1410

1880

2350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0445

Hom.:

Bravo

AF:

0.0870

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 18, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Rubinstein-Taybi syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.55

PhyloP100

-0.50

PromoterAI

0.010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs130018

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over