16-3745291-G-T

Position:

chr16-3745291-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004380.3(CREBBP):c.3900C>A(p.Ile1300=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3 linkuse as main transcript	c.3900C>A	p.Ile1300=	synonymous_variant	22/31	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.3900C>A	p.Ile1300=	synonymous_variant	22/31	1	NM_004380.3	ENSP00000262367	P1	Q92793-1

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

GnomAD3 exomes

AF:

0.0349

AC:

8744

AN:

250754

Hom.:

592

AF XY:

0.0377

AC XY:

5108

AN XY:

135554

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 SAS exome

AF:

0.111

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

Gnomad4 AFR exome

AF:

0.0423

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.00223

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.0253

GnomAD4 genome

AF:

0.0250

AC:

3803

AN:

152318

Hom.:

172

Cov.:

AF XY:

0.0274

AC XY:

2041

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0383

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00981

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

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	-	- -

Rubinstein-Taybi syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2016

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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