16-3745291-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004380.3(CREBBP):c.3900C>A(p.Ile1300Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,613,834 control chromosomes in the GnomAD database, including 1,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 172 hom., cov: 33)

Exomes 𝑓: 0.016 ( 1328 hom. )

Consequence

CREBBP
NM_004380.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.97

Publications

15 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 16-3745291-G-T is Benign according to our data. Variant chr16-3745291-G-T is described in ClinVar as Benign. ClinVar VariationId is 158362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004380.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBBP	NM_004380.3	MANE Select	c.3900C>A	p.Ile1300Ile	synonymous	Exon 22 of 31	NP_004371.2
	CREBBP	NM_001079846.1		c.3786C>A	p.Ile1262Ile	synonymous	Exon 21 of 30	NP_001073315.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CREBBP	ENST00000262367.10	TSL:1 MANE Select	c.3900C>A	p.Ile1300Ile	synonymous	Exon 22 of 31	ENSP00000262367.5
CREBBP	ENST00000382070.7	TSL:1	c.3786C>A	p.Ile1262Ile	synonymous	Exon 21 of 30	ENSP00000371502.3
CREBBP	ENST00000570939.2	TSL:5	c.2535C>A	p.Ile845Ile	synonymous	Exon 17 of 23	ENSP00000461002.2

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3801

AN:

152200

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0349

AC:

8744

AN:

250754

AF XY:

0.0377

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.00993

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0155

AC:

22723

AN:

1461516

Hom.:

1328

Cov.:

AF XY:

0.0183

AC XY:

13275

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.0423

AC:

1417

AN:

33466

American (AMR)

AF:

0.0103

AC:

462

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

305

AN:

26120

East Asian (EAS)

AF:

0.170

AC:

6737

AN:

39680

South Asian (SAS)

AF:

0.109

AC:

9421

AN:

86156

European-Finnish (FIN)

AF:

0.00223

AC:

119

AN:

53412

Middle Eastern (MID)

AF:

0.0251

AC:

145

AN:

5766

European-Non Finnish (NFE)

AF:

0.00233

AC:

2588

AN:

1111856

Other (OTH)

AF:

0.0253

AC:

1529

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

1241

2482

3723

4964

6205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0250

AC:

3803

AN:

152318

Hom.:

172

Cov.:

AF XY:

0.0274

AC XY:

2041

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0383

AC:

1592

AN:

41570

American (AMR)

AF:

0.0170

AC:

260

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

996

AN:

5178

South Asian (SAS)

AF:

0.116

AC:

562

AN:

4826

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00344

AC:

234

AN:

68032

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

185

369

554

738

923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.0263

Asia WGS

AF:

0.137

AC:

475

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00457

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

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

Inborn genetic diseases

Benign:1

Mar 16, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over