rs2965169

Positions:

• chr19-44747899-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017027110.2(BCL3):​c.-94A>C variant causes a 5 prime UTR 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 XM_017027110.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL3	XM_017027110.2	c.-94A>C		5_prime_UTR_variant	1/7		XP_016882599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL3	ENST00000403534.7	n.195A>C		non_coding_transcript_exon_variant	1/8	2
BCL3	ENST00000487394.1	n.64A>C		non_coding_transcript_exon_variant	1/2	3

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

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.429

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

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.508

Alfa AF: 0.435 Hom.: 14753

Bravo AF: 0.518

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2965169; hg19: chr19-45251156; COSMIC: COSV51234737;