rs130021

Positions:

• chr16-3782470-A-G
• chr16-3782470-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004380.3(CREBBP):​c.1573+214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,204 control chromosomes in the GnomAD database, including 6,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6934 hom., cov: 33)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-3782470-A-G is Benign according to our data. Variant chr16-3782470-A-G is described in ClinVar as [Benign]. Clinvar id is 1287666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.1573+214T>C		intron_variant		ENST00000262367.10	NP_004371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREBBP	ENST00000262367.10	c.1573+214T>C		intron_variant		1	NM_004380.3	ENSP00000262367	P1
CREBBP	ENST00000382070.7	c.1459+214T>C		intron_variant		1		ENSP00000371502
CREBBP	ENST00000570939.2	c.178+214T>C		intron_variant		5		ENSP00000461002

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41614 AN: 152086 Hom.: 6933 Cov.: 33

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41615 AN: 152204 Hom.: 6934 Cov.: 33 AF XY: 0.278 AC XY: 20686 AN XY: 74418

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.298

Alfa AF: 0.315 Hom.: 5444

Bravo AF: 0.254

Asia WGS AF: 0.384 AC: 1331 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs130021; hg19: chr16-3832471;