dbSNP rs1461949410: CBFA2T3:p.Arg653Pro (chr16-88876980-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005187.6(CBFA2T3):c.1958G>C(p.Arg653Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000775 in 1,290,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R653H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

CBFA2T3
NM_005187.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23244151).

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.1958G>C	p.Arg653Pro	missense	Exon 12 of 12	NP_005178.4
	CBFA2T3	NM_175931.3		c.1700G>C	p.Arg567Pro	missense	Exon 11 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.1958G>C	p.Arg653Pro	missense	Exon 12 of 12	ENSP00000268679.4	O75081-1
CBFA2T3	ENST00000327483.9	TSL:1	c.1700G>C	p.Arg567Pro	missense	Exon 11 of 11	ENSP00000332122.5	O75081-2
CBFA2T3	ENST00000563856.1	TSL:2	n.925G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.75e-7

AC:

AN:

1290206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

627690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27076

American (AMR)

AF:

0.00

AC:

AN:

21602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19432

East Asian (EAS)

AF:

0.00

AC:

AN:

33570

South Asian (SAS)

AF:

0.00

AC:

AN:

64492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3730

European-Non Finnish (NFE)

AF:

9.66e-7

AC:

AN:

1035320

Other (OTH)

AF:

0.00

AC:

AN:

53720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PhyloP100

0.55

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

REVEL

Benign

0.071

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0020

Vest4

0.37

MutPred

0.29

Gain of catalytic residue at P652 (P = 0.012)

MVP

0.38

MPC

2.1

ClinPred

0.93

GERP RS

2.5

Varity_R

0.40

gMVP

0.50

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

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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