rs130021

Variant names:

• chr16-3782470-A-G
• rs130021
• NM_004380.3:c.1573+214T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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: Illumina, ClinGen
• 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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBBP	NM_004380.3	MANE Select	c.1573+214T>C		intron	N/A	NP_004371.2	Q92793-1
	CREBBP	NM_001079846.1		c.1459+214T>C		intron	N/A	NP_001073315.1	Q92793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBBP	ENST00000262367.10	TSL:1 MANE Select	c.1573+214T>C		intron	N/A	ENSP00000262367.5	Q92793-1
	CREBBP	ENST00000382070.7	TSL:1	c.1459+214T>C		intron	N/A	ENSP00000371502.3	Q92793-2
	CREBBP	ENST00000570939.2	TSL:5	c.178+214T>C		intron	N/A	ENSP00000461002.2	I3L466

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

African (AFR) AF: 0.0825 AC: 3429 AN: 41560

American (AMR) AF: 0.258 AC: 3948 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2103 AN: 5180

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4830

European-Finnish (FIN) AF: 0.386 AC: 4082 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24208 AN: 67990

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.316 Hom.: 7844

Bravo AF: 0.254

Asia WGS AF: 0.384 AC: 1331 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		0.076
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs130021; hg19: chr16-3832471;