Genetic Variant CBFB:c.282+204C>T (chr16-67036959-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.21

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBFB	NM_022845.3 link	c.282+204C>T		intron_variant	Intron 3 of 5	ENST00000412916.7	NP_074036.1	Q13951-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBFB	ENST00000412916.7 link	c.282+204C>T		intron_variant	Intron 3 of 5	1	NM_022845.3	ENSP00000415151.2		Q13951-2

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44127

AN:

151384

Hom.:

6881

Cov.:

show subpopulations

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.:

AF XY:

0.296

AC XY:

21852

AN XY:

73938

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.296

Hom.:

870

Bravo

AF:

0.285

Asia WGS

AF:

0.369

AC:

1284

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.30

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over