19-44756336-G-C

Variant names:

• chr19-44756336-G-C
• NM_005178.5:c.515G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005178.5(BCL3):​c.515G>C​(p.Arg172Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000742 in 1,348,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: BCL3 NM_005178.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.22

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL3	NM_005178.5	c.515G>C	p.Arg172Pro	missense_variant	Exon 3 of 9	ENST00000164227.10	NP_005169.2
BCL3	XM_011527198.4	c.515G>C	p.Arg172Pro	missense_variant	Exon 3 of 9		XP_011525500.3
BCL3	XM_017027110.2	c.395G>C	p.Arg132Pro	missense_variant	Exon 3 of 7		XP_016882599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL3	ENST00000164227.10	c.515G>C	p.Arg172Pro	missense_variant	Exon 3 of 9	1	NM_005178.5	ENSP00000164227.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.42e-7 AC: 1 AN: 1348378 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 665438

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.52e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	0.97
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.016
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.40
Sift	Benign	0.13	T
Sift4G	Benign	0.44	T
Polyphen		0.0050	B
Vest4		0.86
MutPred		0.60		Gain of glycosylation at P175 (P = 0.0674);
MVP		0.93
MPC		1.9
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.86
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45259593;