Genetic Variant BCL3:p.Arg3Pro (chr19-44748798-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005178.5(BCL3):c.8G>C(p.Arg3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R3Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BCL3
NM_005178.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Publications

0 publications found

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]

BCL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL3	NM_005178.5	MANE Select	c.8G>C	p.Arg3Pro	missense	Exon 1 of 9	NP_005169.2	P20749

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL3	ENST00000164227.10	TSL:1 MANE Select	c.8G>C	p.Arg3Pro	missense	Exon 1 of 9	ENSP00000164227.5	P20749
BCL3	ENST00000487394.1	TSL:3	n.397G>C		non_coding_transcript_exon	Exon 2 of 2
BCL3	ENST00000403534.7	TSL:2	n.424+670G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

959510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

450844

African (AFR)

AF:

0.00

AC:

AN:

18706

American (AMR)

AF:

0.00

AC:

AN:

4636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9260

East Asian (EAS)

AF:

0.00

AC:

AN:

15476

South Asian (SAS)

AF:

0.00

AC:

AN:

18442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2262

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842882

Other (OTH)

AF:

0.00

AC:

AN:

34990

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.66

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.81

PhyloP100

1.9

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.30

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.36

MutPred

0.38

Gain of catalytic residue at R3 (P = 0.0065)

MVP

0.73

MPC

0.75

ClinPred

0.78

GERP RS

2.8

PromoterAI

0.022

Neutral

(source)

Varity_R

0.24

gMVP

0.42

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over