Genetic Variant NM_005178.5:c.182G>A (chr19-44748972-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005178.5(BCL3):c.182G>A(p.Arg61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,374,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

BCL3
NM_005178.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.128

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

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08270672).

BS2

High AC in GnomAd4 at 7 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.182G>A	p.Arg61His	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.182G>A	p.Arg61His	missense	Exon 1 of 9	ENSP00000164227.5	P20749
BCL3	ENST00000487394.1	TSL:3	n.571G>A		non_coding_transcript_exon	Exon 2 of 2
BCL3	ENST00000403534.7	TSL:2	n.424+844G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

44740

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000573

AC:

AN:

1222654

Hom.:

Cov.:

AF XY:

0.00000500

AC XY:

AN XY:

600408

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24314

American (AMR)

AF:

0.00

AC:

AN:

17834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19282

East Asian (EAS)

AF:

0.00

AC:

AN:

26734

South Asian (SAS)

AF:

0.00

AC:

AN:

59692

European-Finnish (FIN)

AF:

0.0000347

AC:

AN:

28854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3494

European-Non Finnish (NFE)

AF:

0.00000604

AC:

AN:

993430

Other (OTH)

AF:

0.00

AC:

AN:

49020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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

AF:

0.0000462

AC:

AN:

151406

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73926

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41356

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67758

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

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:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000180

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.62

M_CAP

Benign

0.069

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.13

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.080

REVEL

Benign

0.087

Sift

Uncertain

0.019

Sift4G

Benign

0.31

Polyphen

0.0020

Vest4

0.065

MutPred

0.35

Loss of helix (P = 0.0033)

MVP

0.30

MPC

0.33

ClinPred

0.19

GERP RS

2.5

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.043

gMVP

0.27

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over