rs55960450

Positions:

chr16-3728426-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004380.3(CREBBP):c.6621A>G(p.Gln2207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,612,396 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 32)

Exomes 𝑓: 0.012 ( 267 hom. )

Consequence

CREBBP
NM_004380.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0870

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-3728426-T-C is Benign according to our data. Variant chr16-3728426-T-C is described in ClinVar as [Benign]. Clinvar id is 95063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0511 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.6621A>G	p.Gln2207=	synonymous_variant	31/31	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.6621A>G	p.Gln2207=	synonymous_variant	31/31	1	NM_004380.3	ENSP00000262367	P1	Q92793-1
CREBBP	ENST00000382070.7 linkuse as main transcript	c.6507A>G	p.Gln2169=	synonymous_variant	30/30	1		ENSP00000371502		Q92793-2

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1914

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00964

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0564

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00718

Gnomad OTH

AF:

0.0159

GnomAD3 exomes

AF:

0.0157

AC:

3847

AN:

245396

Hom.:

AF XY:

0.0178

AC XY:

2377

AN XY:

133306

show subpopulations

Gnomad AFR exome

AF:

0.0178

Gnomad AMR exome

AF:

0.00576

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.0156

Gnomad SAS exome

AF:

0.0523

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.00830

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0120

AC:

17489

AN:

1460568

Hom.:

267

Cov.:

AF XY:

0.0133

AC XY:

9696

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.00600

Gnomad4 ASJ exome

AF:

0.0465

Gnomad4 EAS exome

AF:

0.0211

Gnomad4 SAS exome

AF:

0.0519

Gnomad4 FIN exome

AF:

0.00186

Gnomad4 NFE exome

AF:

0.00798

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.0126

AC:

1914

AN:

151828

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

968

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.00963

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0566

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00718

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0131

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 18, 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

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 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

-0.75

CADD

Benign

0.029

DANN

Benign

0.23

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