19-44750911-C-A

Position:

• chr19-44750911-C-A

Variant summary

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

The NM_005178.5(BCL3):​c.257-316C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,178 control chromosomes in the GnomAD database, including 885 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 0.090 (885 hom., cov: 32)
• Consequence: BCL3 NM_005178.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL3	NM_005178.5	c.257-316C>A		intron_variant		ENST00000164227.10	NP_005169.2
BCL3	XM_011527198.4	c.257-316C>A		intron_variant			XP_011525500.3
BCL3	XM_017027110.2	c.137-316C>A		intron_variant			XP_016882599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL3	ENST00000164227.10	c.257-316C>A		intron_variant		1	NM_005178.5	ENSP00000164227	P1
BCL3	ENST00000403534.7	n.425-316C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13652 AN: 152060 Hom.: 884 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0836

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0897 AC: 13653 AN: 152178 Hom.: 885 Cov.: 32 AF XY: 0.0898 AC XY: 6682 AN XY: 74378

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.110 Hom.: 457

Bravo AF: 0.0773

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs8103315; hg19: chr19-45254168;