rs7198381

Variant names:

• chr16-3814501-A-G
• rs7198381
• NM_004380.3:c.799-3722T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3814501-A-G
• chr16-3814501-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004380.3(CREBBP):​c.799-3722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,860 control chromosomes in the GnomAD database, including 3,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (3326 hom., cov: 31)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 1 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: 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 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.799-3722T>C		intron	N/A	NP_004371.2
	CREBBP	NM_001079846.1		c.799-3722T>C		intron	N/A	NP_001073315.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBBP	ENST00000262367.10	TSL:1 MANE Select	c.799-3722T>C		intron	N/A	ENSP00000262367.5
	CREBBP	ENST00000382070.7	TSL:1	c.799-3722T>C		intron	N/A	ENSP00000371502.3
	CREBBP	ENST00000636895.1	TSL:5	n.26-1429T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19983 AN: 151742 Hom.: 3301 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.00331

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.132 AC: 20051 AN: 151860 Hom.: 3326 Cov.: 31 AF XY: 0.130 AC XY: 9624 AN XY: 74234

African (AFR) AF: 0.383 AC: 15826 AN: 41348

American (AMR) AF: 0.0679 AC: 1037 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1071 AN: 5140

South Asian (SAS) AF: 0.135 AC: 649 AN: 4798

European-Finnish (FIN) AF: 0.00331 AC: 35 AN: 10576

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 859 AN: 67960

Other (OTH) AF: 0.118 AC: 248 AN: 2096

Alfa AF: 0.0797 Hom.: 237

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.21
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7198381; hg19: chr16-3864502;