rs8100239

Variant names:

• chr19-44749847-T-A
• rs8100239
• NM_005178.5:c.256+801T>A

Variant summary

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

The NM_005178.5(BCL3):​c.256+801T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,788 control chromosomes in the GnomAD database, including 11,377 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 0.38 (11377 hom., cov: 31)
• Consequence: BCL3 NM_005178.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL3	NM_005178.5	c.256+801T>A		intron_variant	Intron 1 of 8	ENST00000164227.10	NP_005169.2
BCL3	XM_011527198.4	c.256+801T>A		intron_variant	Intron 1 of 8		XP_011525500.3
BCL3	XM_017027110.2	c.137-1380T>A		intron_variant	Intron 1 of 6		XP_016882599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL3	ENST00000164227.10	c.256+801T>A		intron_variant	Intron 1 of 8	1	NM_005178.5	ENSP00000164227.5
BCL3	ENST00000403534.7	n.425-1380T>A		intron_variant	Intron 1 of 7	2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57981 AN: 151670 Hom.: 11361 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.382 AC: 58041 AN: 151788 Hom.: 11377 Cov.: 31 AF XY: 0.382 AC XY: 28320 AN XY: 74164

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.415

Alfa AF: 0.360 Hom.: 1392

Bravo AF: 0.393

Asia WGS AF: 0.351 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs8100239; hg19: chr19-45253104;