Genetic Variant BCL3:c.*103_*104dupCC (chr19-44759707-G-GCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is . The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005178.5(BCL3):c.*103_*104dupCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0020 ( 0 hom. )

Consequence

BCL3
NM_005178.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.398

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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005178.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 171 AD gene.

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.103_104dupCC		3_prime_UTR	Exon 9 of 9	NP_005169.2	P20749

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCL3	ENST00000164227.10	TSL:1 MANE Select	c.103_104dupCC	3_prime_UTR	Exon 9 of 9	ENSP00000164227.5	P20749
BCL3	ENST00000474300.1	TSL:2	n.712_713dupCC	non_coding_transcript_exon	Exon 4 of 4
BCL3	ENST00000444487.1	TSL:5	c.244_245insCC	downstream_gene	N/A	ENSP00000393731.1	H7C0A2

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

171

AN:

111356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000840

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00417

Gnomad SAS

AF:

0.000287

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00198

AC:

850

AN:

428930

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

465

AN XY:

224688

show subpopulations

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

African (AFR)

AF:

0.00297

AC:

AN:

10792

American (AMR)

AF:

0.00225

AC:

AN:

14202

Ashkenazi Jewish (ASJ)

AF:

0.00160

AC:

AN:

12490

East Asian (EAS)

AF:

0.00223

AC:

AN:

25106

South Asian (SAS)

AF:

0.000740

AC:

AN:

40566

European-Finnish (FIN)

AF:

0.000760

AC:

AN:

27640

Middle Eastern (MID)

AF:

0.00160

AC:

AN:

1870

European-Non Finnish (NFE)

AF:

0.00220

AC:

599

AN:

271862

Other (OTH)

AF:

0.00234

AC:

AN:

24402

⚠️ 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: 0.283

Heterozygous variant carriers

137

206

274

343

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

AF:

0.00153

AC:

171

AN:

111456

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

AN XY:

52758

show subpopulations

African (AFR)

AF:

0.00210

AC:

AN:

32868

American (AMR)

AF:

0.000840

AC:

AN:

10718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2618

East Asian (EAS)

AF:

0.00418

AC:

AN:

3352

South Asian (SAS)

AF:

0.000287

AC:

AN:

3482

European-Finnish (FIN)

AF:

0.00103

AC:

AN:

5804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

50334

Other (OTH)

AF:

0.00

AC:

AN:

1476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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19-44759707-GCCCCC-GCCCCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over