rs2526690

Positions:

• chr16-3867530-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004380.3(CREBBP):​c.85+12302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,058 control chromosomes in the GnomAD database, including 59,711 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 0.87 (59711 hom., cov: 30)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.85+12302T>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.85+12302T>C		intron_variant		1	NM_004380.3	ENSP00000262367.5
CREBBP	ENST00000382070.7	c.85+12302T>C		intron_variant		1		ENSP00000371502.3

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132548 AN: 151940 Hom.: 59696 Cov.: 30

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.872 AC: 132597 AN: 152058 Hom.: 59711 Cov.: 30 AF XY: 0.874 AC XY: 65024 AN XY: 74372

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.886

Alfa AF: 0.922 Hom.: 8195

Bravo AF: 0.855

Asia WGS AF: 0.815 AC: 2835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.66

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: rs2526690; hg19: chr16-3917531;