rs8103315

Variant names:

• chr19-44750911-C-A
• rs8103315
• NM_005178.5:c.257-316C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005178.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL3	NM_005178.5	MANE Select	c.257-316C>A		intron	N/A	NP_005169.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL3	ENST00000164227.10	TSL:1 MANE Select	c.257-316C>A		intron	N/A	ENSP00000164227.5
	BCL3	ENST00000403534.7	TSL:2	n.425-316C>A		intron	N/A

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

African (AFR) AF: 0.0230 AC: 955 AN: 41528

American (AMR) AF: 0.0629 AC: 961 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2153 AN: 10560

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8865 AN: 68002

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.115 Hom.: 550

Bravo AF: 0.0773

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.64
PhyloP100		0.29
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8103315; hg19: chr19-45254168;