19-44748920-C-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_005178.5(BCL3):c.130C>A(p.Pro44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,170,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)
Exomes 𝑓: 9.8e-7 ( 0 hom. )
Consequence
BCL3
NM_005178.5 missense
NM_005178.5 missense
Scores
3
3
12
Clinical Significance
Conservation
PhyloP100: 2.29
Publications
0 publications found
Genes affected
BCL3 (HGNC:998): (BCL3 transcription coactivator) This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional co-activator that activates through its association with NF-kappa B homodimers. The expression of this gene can be induced by NF-kappa B, which forms a part of the autoregulatory loop that controls the nuclear residence of p50 NF-kappa B. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4135273).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005178.5. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
Frequencies
GnomAD3 genomes 0.00000668 AC: 1AN: 149598Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
149598
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 9.79e-7 AC: 1AN: 1021384Hom.: 0 Cov.: 30 AF XY: 0.00000206 AC XY: 1AN XY: 484406 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1021384
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
484406
show subpopulations
African (AFR)
AF:
AC:
0
AN:
20460
American (AMR)
AF:
AC:
1
AN:
6782
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
11414
East Asian (EAS)
AF:
AC:
0
AN:
19894
South Asian (SAS)
AF:
AC:
0
AN:
20936
European-Finnish (FIN)
AF:
AC:
0
AN:
17696
Middle Eastern (MID)
AF:
AC:
0
AN:
2576
European-Non Finnish (NFE)
AF:
AC:
0
AN:
882826
Other (OTH)
AF:
AC:
0
AN:
38800
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000668 AC: 1AN: 149598Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1AN XY: 72976 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
149598
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
72976
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41108
American (AMR)
AF:
AC:
0
AN:
15072
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3440
East Asian (EAS)
AF:
AC:
0
AN:
5074
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
9630
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67168
Other (OTH)
AF:
AC:
0
AN:
2062
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.002)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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