Genetic Variant NM_005178.5:c.214C>A (chr19-44749004-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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. P72S) has been classified as Uncertain significance.

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

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

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.214C>A	p.Pro72Thr	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.214C>A	p.Pro72Thr	missense	Exon 1 of 9	ENSP00000164227.5	P20749
BCL3	ENST00000487394.1	TSL:3	n.603C>A		splice_region non_coding_transcript_exon	Exon 2 of 2
BCL3	ENST00000403534.7	TSL:2	n.424+876C>A		intron	N/A

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24746

American (AMR)

AF:

0.00

AC:

AN:

18532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19416

East Asian (EAS)

AF:

0.00

AC:

AN:

27258

South Asian (SAS)

AF:

0.00

AC:

AN:

59576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3580

European-Non Finnish (NFE)

AF:

0.00000100

AC:

AN:

998314

Other (OTH)

AF:

0.00

AC:

AN:

49674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

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

PhyloP100

0.29

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

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.33

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over