chr19-44748998-C-T

Variant names:

• chr19-44748998-C-T
• NM_005178.5:c.208C>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.208C>T​(p.Pro70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCL3 NM_005178.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• 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=0.1362251).

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.208C>T	p.Pro70Ser	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.208C>T	p.Pro70Ser	missense	Exon 1 of 9	ENSP00000164227.5	P20749
	BCL3	ENST00000487394.1	TSL:3	n.597C>T		non_coding_transcript_exon	Exon 2 of 2
	BCL3	ENST00000403534.7	TSL:2	n.424+870C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1233554 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 605842

African (AFR) AF: 0.00 AC: 0 AN: 24812

American (AMR) AF: 0.00 AC: 0 AN: 18610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19664

East Asian (EAS) AF: 0.00 AC: 0 AN: 27380

South Asian (SAS) AF: 0.00 AC: 0 AN: 60008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1000396

Other (OTH) AF: 0.00 AC: 0 AN: 49874

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.050
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.031	D
Polyphen		0.0030	B
Vest4		0.098
MutPred		0.40		Gain of glycosylation at P70 (P = 0.0116)
MVP		0.43
MPC		0.15
ClinPred		0.12	T
GERP RS		2.7
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.34
Mutation Taster		=98/2	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

hg19: chr19-45252255;