chr16-3727689-GA-G

Position:

• chr16-3727689-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004380.3(CREBBP):​c.*28del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00692 in 1,613,786 control chromosomes in the GnomAD database, including 510 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (263 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (247 hom.)
• Consequence: CREBBP NM_004380.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.60

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 -10 ACMG points.

• BP6: Variant 16-3727689-GA-G is Benign according to our data. Variant chr16-3727689-GA-G is described in ClinVar as [Benign]. Clinvar id is 1292986.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBBP	NM_004380.3	c.*28del		3_prime_UTR_variant	31/31	ENST00000262367.10	NP_004371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREBBP	ENST00000262367.10	c.*28del		3_prime_UTR_variant	31/31	1	NM_004380.3	ENSP00000262367	P1
CREBBP	ENST00000382070.7	c.*28del		3_prime_UTR_variant	30/30	1		ENSP00000371502

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5159 AN: 151946 Hom.: 263 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00987 AC: 2479 AN: 251172 Hom.: 129 AF XY: 0.00702 AC XY: 953 AN XY: 135786

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.00893

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000880

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00410 AC: 5987 AN: 1461722 Hom.: 247 Cov.: 32 AF XY: 0.00354 AC XY: 2574 AN XY: 727166

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.00973

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000658

Gnomad4 OTH exome AF: 0.00979

GnomAD4 genome AF: 0.0340 AC: 5173 AN: 152064 Hom.: 263 Cov.: 31 AF XY: 0.0320 AC XY: 2377 AN XY: 74326

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.00405

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000853

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00210 Hom.: 2

Bravo AF: 0.0385

Asia WGS AF: 0.00696 AC: 25 AN: 3464

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

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

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: rs142721165; hg19: chr16-3777690;