Genetic Variant BCL3:c.*103_*104delCC (chr19-44759707-GCC-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is . The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_005178.5(BCL3):c.*103_*104delCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 538,024 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0056 ( 10 hom., cov: 0)

Exomes 𝑓: 0.0036 ( 2 hom. )

Consequence

BCL3
NM_005178.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.715

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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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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00557 (621/111446) while in subpopulation AFR AF = 0.0174 (573/32864). AF 95% confidence interval is 0.0163. There are 10 homozygotes in GnomAd4. There are 272 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 621 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_104delCC		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_104delCC	3_prime_UTR	Exon 9 of 9	ENSP00000164227.5	P20749
BCL3	ENST00000474300.1	TSL:2	n.712_713delCC	non_coding_transcript_exon	Exon 4 of 4
BCL3	ENST00000444487.1	TSL:5	c.245_246delCC	downstream_gene	N/A	ENSP00000393731.1	H7C0A2

Frequencies

GnomAD3 genomes

AF:

0.00549

AC:

611

AN:

111346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00252

Gnomad ASJ

AF:

0.000382

Gnomad EAS

AF:

0.000298

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000358

Gnomad OTH

AF:

0.000687

GnomAD4 exome

AF:

0.00358

AC:

1528

AN:

426578

Hom.:

AF XY:

0.00347

AC XY:

776

AN XY:

223334

show subpopulations

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

African (AFR)

AF:

0.0216

AC:

232

AN:

10752

American (AMR)

AF:

0.00497

AC:

AN:

14076

Ashkenazi Jewish (ASJ)

AF:

0.00362

AC:

AN:

12434

East Asian (EAS)

AF:

0.00397

AC:

AN:

24948

South Asian (SAS)

AF:

0.00462

AC:

186

AN:

40238

European-Finnish (FIN)

AF:

0.00128

AC:

AN:

27446

Middle Eastern (MID)

AF:

0.00325

AC:

AN:

1848

European-Non Finnish (NFE)

AF:

0.00280

AC:

757

AN:

270572

Other (OTH)

AF:

0.00404

AC:

AN:

24264

⚠️ 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: 0.320

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00557

AC:

621

AN:

111446

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

272

AN XY:

52746

show subpopulations

African (AFR)

AF:

0.0174

AC:

573

AN:

32864

American (AMR)

AF:

0.00252

AC:

AN:

10718

Ashkenazi Jewish (ASJ)

AF:

0.000382

AC:

AN:

2618

East Asian (EAS)

AF:

0.000299

AC:

AN:

3348

South Asian (SAS)

AF:

0.00

AC:

AN:

3480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.000358

AC:

AN:

50336

Other (OTH)

AF:

0.000677

AC:

AN:

1478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

0.71

Mutation Taster

=100/0

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

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

Publications

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19-44759707-GCCCCC-GCCC

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