dbSNP rs1445898429: BCL3:p.Pro72Thr (chr19-44749004-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005178.5(BCL3):c.214C>A(p.Pro72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,230,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

BCL3
NM_005178.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.291

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22420067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL3	NM_005178.5 link	c.214C>A	p.Pro72Thr	missense_variant	Exon 1 of 9	ENST00000164227.10	NP_005169.2
BCL3	XM_011527198.4 link	c.214C>A	p.Pro72Thr	missense_variant	Exon 1 of 9		XP_011525500.3
BCL3	XM_017027110.2 link	c.136+876C>A		intron_variant	Intron 1 of 6		XP_016882599.1	B7Z3N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCL3	ENST00000164227.10 link	c.214C>A	p.Pro72Thr	missense_variant	Exon 1 of 9	1	NM_005178.5	ENSP00000164227.5	P20749
BCL3	ENST00000487394.1 link	n.603C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	3
BCL3	ENST00000403534.7 link	n.424+876C>A		intron_variant	Intron 1 of 7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.13e-7

AC:

AN:

1230144

Hom.:

Cov.:

AF XY:

0.00000166

AC XY:

AN XY:

603908

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:

0.00000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.076

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.41

REVEL

Benign

0.093

Sift

Benign

0.048

Sift4G

Uncertain

0.0090

Polyphen

0.61

Vest4

0.18

MutPred

0.42

Gain of phosphorylation at P72 (P = 0.0101);

MVP

0.73

MPC

0.16

ClinPred

0.20

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over