rs2965169

Variant names:

• chr19-44747899-A-C
• rs2965169
• XM_017027110.2:c.-94A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000403534.7(BCL3):​n.195A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,137,970 control chromosomes in the GnomAD database, including 101,114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19811 hom., cov: 31)
  • Exomes 𝑓: 0.40 (81303 hom.)
• Consequence: BCL3 ENST00000403534.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 35 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]

ENSG00000302962 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000403534.7. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL3	ENST00000403534.7	TSL:2	n.195A>C		non_coding_transcript_exon	Exon 1 of 8
	BCL3	ENST00000487394.1	TSL:3	n.64A>C		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000302962	ENST00000790732.1		n.465T>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74926 AN: 151616 Hom.: 19775 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.400 AC: 394364 AN: 986234 Hom.: 81303 Cov.: 30 AF XY: 0.402 AC XY: 188180 AN XY: 468388

African (AFR) AF: 0.712 AC: 13943 AN: 19582

American (AMR) AF: 0.556 AC: 3799 AN: 6828

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 5589 AN: 10266

East Asian (EAS) AF: 0.370 AC: 5426 AN: 14684

South Asian (SAS) AF: 0.473 AC: 21710 AN: 45898

European-Finnish (FIN) AF: 0.349 AC: 1854 AN: 5310

Middle Eastern (MID) AF: 0.501 AC: 1099 AN: 2192

European-Non Finnish (NFE) AF: 0.385 AC: 325506 AN: 845520

Other (OTH) AF: 0.429 AC: 15438 AN: 35954

GnomAD4 genome AF: 0.494 AC: 75013 AN: 151736 Hom.: 19811 Cov.: 31 AF XY: 0.493 AC XY: 36536 AN XY: 74168

African (AFR) AF: 0.687 AC: 28475 AN: 41420

American (AMR) AF: 0.549 AC: 8389 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1902 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2051 AN: 5110

South Asian (SAS) AF: 0.491 AC: 2363 AN: 4810

European-Finnish (FIN) AF: 0.347 AC: 3644 AN: 10514

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26652 AN: 67822

Other (OTH) AF: 0.508 AC: 1072 AN: 2112

Alfa AF: 0.448 Hom.: 22359

Bravo AF: 0.518

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.56
PhyloP100		-1.2

Splicing

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.

Other links and lift over

dbSNP: rs2965169;

hg19: chr19-45251156;

COSMIC: COSV51234737;