chr16-3778347-A-G

Position:

• chr16-3778347-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004380.3(CREBBP):​c.1942-165T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 152,268 control chromosomes in the GnomAD database, including 754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.082 (754 hom., cov: 32)
• Consequence: CREBBP NM_004380.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.287

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-3778347-A-G is Benign according to our data. Variant chr16-3778347-A-G is described in ClinVar as [Benign]. Clinvar id is 1239359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.1942-165T>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.1942-165T>C		intron_variant		1	NM_004380.3	ENSP00000262367.5

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12552 AN: 152150 Hom.: 752 Cov.: 32

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0825 AC: 12560 AN: 152268 Hom.: 754 Cov.: 32 AF XY: 0.0844 AC XY: 6284 AN XY: 74444

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0648

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.110

Alfa AF: 0.103 Hom.: 1453

Bravo AF: 0.0786

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.64

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: rs130005; hg19: chr16-3828348;