19-44749026-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005178.5(BCL3):​c.236C>T​(p.Pro79Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,361,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

BCL3
NM_005178.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.754
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.27157065).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BCL3NM_005178.5 linkuse as main transcriptc.236C>T p.Pro79Leu missense_variant 1/9 ENST00000164227.10 NP_005169.2
BCL3XM_011527198.4 linkuse as main transcriptc.236C>T p.Pro79Leu missense_variant 1/9 XP_011525500.3
BCL3XM_017027110.2 linkuse as main transcriptc.136+898C>T intron_variant XP_016882599.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BCL3ENST00000164227.10 linkuse as main transcriptc.236C>T p.Pro79Leu missense_variant 1/91 NM_005178.5 ENSP00000164227 P1
BCL3ENST00000403534.7 linkuse as main transcriptn.424+898C>T intron_variant, non_coding_transcript_variant 2
BCL3ENST00000487394.1 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151888
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000413
AC:
5
AN:
1210084
Hom.:
0
Cov.:
30
AF XY:
0.00000337
AC XY:
2
AN XY:
592680
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000150
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:
0.00000302
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151888
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000113
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 24, 2023The c.236C>T (p.P79L) alteration is located in exon 1 (coding exon 1) of the BCL3 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the proline (P) at amino acid position 79 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.082
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.69
T
M_CAP
Pathogenic
0.32
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.70
N
REVEL
Benign
0.14
Sift
Benign
0.036
D
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.15
MutPred
0.32
Loss of disorder (P = 0.0176);
MVP
0.71
MPC
0.44
ClinPred
0.66
D
GERP RS
3.8
Varity_R
0.074
gMVP
0.29

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.

Other links and lift over

dbSNP: rs779203246; hg19: chr19-45252283; API