NM_022845.3:c.282+204C>T

Variant names:

• chr16-67036959-C-T
• rs8051487
• NM_022845.3:c.282+204C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022845.3(CBFB):​c.282+204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,502 control chromosomes in the GnomAD database, including 6,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6884 hom., cov: 31)
• Consequence: CBFB NM_022845.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21
• Publications: 4 publications found

Genes affected

CBFB (HGNC:1539): (core-binding factor subunit beta) The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). The beta subunit is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CBFB Gene-Disease associations (from GenCC):

• cleidocranial dysplasia 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• acute myeloid leukemia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 16-67036959-C-T is Benign according to our data. Variant chr16-67036959-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBFB	NM_022845.3	MANE Select	c.282+204C>T		intron	N/A	NP_074036.1	Q13951-2
	CBFB	NM_001755.3		c.282+204C>T		intron	N/A	NP_001746.1	Q13951-1
	CBFB	NM_001368707.1		c.165+7146C>T		intron	N/A	NP_001355636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBFB	ENST00000412916.7	TSL:1 MANE Select	c.282+204C>T		intron	N/A	ENSP00000415151.2	Q13951-2
	CBFB	ENST00000290858.11	TSL:1	c.282+204C>T		intron	N/A	ENSP00000290858.6	Q13951-1
	CBFB	ENST00000565389.1	TSL:1	c.111+7146C>T		intron	N/A	ENSP00000462932.1	J3KTD8

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44127 AN: 151384 Hom.: 6881 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.291 AC: 44138 AN: 151502 Hom.: 6884 Cov.: 31 AF XY: 0.296 AC XY: 21852 AN XY: 73938

African (AFR) AF: 0.168 AC: 6939 AN: 41266

American (AMR) AF: 0.330 AC: 5024 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1808 AN: 5148

South Asian (SAS) AF: 0.375 AC: 1795 AN: 4790

European-Finnish (FIN) AF: 0.324 AC: 3378 AN: 10432

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22572 AN: 67884

Other (OTH) AF: 0.330 AC: 689 AN: 2090

Alfa AF: 0.296 Hom.: 870

Bravo AF: 0.285

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.70
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8051487; hg19: chr16-67070862; COSMIC: COSV52002855;