rs62039107

Positions:

• chr16-3840292-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004380.3(CREBBP):​c.798+10005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,150 control chromosomes in the GnomAD database, including 4,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.21 (4454 hom., cov: 31)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-3840292-A-G is Benign according to our data. Variant chr16-3840292-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.798+10005T>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.798+10005T>C		intron_variant		1	NM_004380.3	ENSP00000262367.5
CREBBP	ENST00000382070.7	c.798+10005T>C		intron_variant		1		ENSP00000371502.3
CREBBP	ENST00000636895.1	n.25+10005T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32491 AN: 152032 Hom.: 4456 Cov.: 31

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.214 AC: 32492 AN: 152150 Hom.: 4454 Cov.: 31 AF XY: 0.211 AC XY: 15665 AN XY: 74372

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.0950

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.206

Alfa AF: 0.256 Hom.: 766

Bravo AF: 0.209

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.30

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: rs62039107; hg19: chr16-3890293;