rs2965169

Variant names:

• chr19-44747899-A-C
• rs2965169
• ENST00000403534.7:n.195A>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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL3	XM_017027110.2	c.-94A>C		5_prime_UTR_variant	Exon 1 of 7		XP_016882599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL3	ENST00000403534.7	n.195A>C		non_coding_transcript_exon_variant	Exon 1 of 8	2
BCL3	ENST00000487394.1	n.64A>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000302962	ENST00000790732.1	n.465T>G		non_coding_transcript_exon_variant	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 v4.3

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

Other links and lift over

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