rs756757934

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005187.6(CBFA2T3):​c.1367G>T​(p.Arg456Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,433,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R456H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CBFA2T3
NM_005187.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051306546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBFA2T3NM_005187.6 linkc.1367G>T p.Arg456Leu missense_variant Exon 9 of 12 ENST00000268679.9 NP_005178.4 O75081-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBFA2T3ENST00000268679.9 linkc.1367G>T p.Arg456Leu missense_variant Exon 9 of 12 1 NM_005187.6 ENSP00000268679.4 O75081-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1433840
Hom.:
0
Cov.:
32
AF XY:
0.00000141
AC XY:
1
AN XY:
710968
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.10e-7
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
13
DANN
Benign
0.95
DEOGEN2
Benign
0.082
.;T;T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.051
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.6
.;N;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.53
N;N;N
REVEL
Benign
0.060
Sift
Benign
0.66
T;T;T
Sift4G
Benign
0.71
T;T;.
Polyphen
0.0
B;B;.
Vest4
0.12
MutPred
0.26
.;Loss of solvent accessibility (P = 0.0364);.;
MVP
0.36
MPC
0.077
ClinPred
0.29
T
GERP RS
2.6
Varity_R
0.067
gMVP
0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88947734; API