rs7198381

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.799-3722T>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.799-3722T>C		intron_variant		1	NM_004380.3	ENSP00000262367.5
CREBBP	ENST00000382070.7	c.799-3722T>C		intron_variant		1		ENSP00000371502.3
CREBBP	ENST00000636895.1	n.26-1429T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.00331

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0797 Hom.: 237

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7198381; hg19: chr16-3864502;