dbSNP rs756757934: CBFA2T3:p.Arg456His (chr16-88881326-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005187.6(CBFA2T3):c.1367G>A(p.Arg456His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,433,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CBFA2T3
NM_005187.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Publications

1 publications found

Variant links:

Genes affected

CBFA2T3 (HGNC:1537): (CBFA2/RUNX1 partner transcriptional co-repressor 3) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(16;21)(q24;q22) translocation is one of the less common karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. This gene is also a putative breast tumor suppressor. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

CBFA2T3 links:

ENSG00000259881 (HGNC:):

ENSG00000259881 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03781855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005187.6. 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
	CBFA2T3	NM_005187.6	MANE Select	c.1367G>A	p.Arg456His	missense	Exon 9 of 12	NP_005178.4
	CBFA2T3	NM_175931.3		c.1109G>A	p.Arg370His	missense	Exon 8 of 11	NP_787127.1	O75081-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBFA2T3	ENST00000268679.9	TSL:1 MANE Select	c.1367G>A	p.Arg456His	missense	Exon 9 of 12	ENSP00000268679.4	O75081-1
CBFA2T3	ENST00000327483.9	TSL:1	c.1109G>A	p.Arg370His	missense	Exon 8 of 11	ENSP00000332122.5	O75081-2
CBFA2T3	ENST00000569464.5	TSL:1	c.1184G>A	p.Arg395His	missense	Exon 9 of 10	ENSP00000454851.1	H3BNH2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000958

AC:

AN:

208744

AF XY:

0.0000174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000188

AC:

AN:

1433840

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

710968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32910

American (AMR)

AF:

0.00

AC:

AN:

42300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25478

East Asian (EAS)

AF:

0.00

AC:

AN:

38722

South Asian (SAS)

AF:

0.000107

AC:

AN:

84036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0000164

AC:

AN:

1099270

Other (OTH)

AF:

0.00

AC:

AN:

59174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000296

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000170

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.038

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

PhyloP100

1.6

PrimateAI

Benign

0.34

PROVEAN

Benign

1.5

REVEL

Benign

0.038

Sift

Benign

0.76

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.079

MutPred

0.20

Gain of glycosylation at S457 (P = 0.0779)

MVP

0.27

MPC

0.077

ClinPred

0.11

GERP RS

2.6

Varity_R

0.024

gMVP

0.24

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over