19-44748942-C-T

Variant names:

• chr19-44748942-C-T
• rs768745302
• NM_005178.5:c.152C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005178.5(BCL3):​c.152C>T​(p.Ala51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000922 in 1,084,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A51E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: BCL3 NM_005178.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 0 publications found

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]

ACMG classification

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=0.10489243).

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.152C>T	p.Ala51Val	missense	Exon 1 of 9	NP_005169.2	P20749

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL3	ENST00000164227.10	TSL:1 MANE Select	c.152C>T	p.Ala51Val	missense	Exon 1 of 9	ENSP00000164227.5	P20749
	BCL3	ENST00000487394.1	TSL:3	n.541C>T		non_coding_transcript_exon	Exon 2 of 2
	BCL3	ENST00000403534.7	TSL:2	n.424+814C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.22e-7 AC: 1 AN: 1084606 Hom.: 0 Cov.: 30 AF XY: 0.00000192 AC XY: 1 AN XY: 520214

African (AFR) AF: 0.00 AC: 0 AN: 21890

American (AMR) AF: 0.00 AC: 0 AN: 9776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14386

East Asian (EAS) AF: 0.00 AC: 0 AN: 23800

South Asian (SAS) AF: 0.00 AC: 0 AN: 30310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2858

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 917970

Other (OTH) AF: 0.00 AC: 0 AN: 42342

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.17
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.068	T
Polyphen		0.0010	B
Vest4		0.065
MutPred		0.34		Loss of loop (P = 0.0031)
MVP		0.49
MPC		0.14
ClinPred		0.17	T
GERP RS		-0.090
PromoterAI		0.048	Neutral
Varity_R		0.079
gMVP		0.25
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs768745302; hg19: chr19-45252199;