NM_001706.5:c.-50+5077G>C

Variant names:

• chr3-187740333-C-G
• rs3774303
• NM_001706.5:c.-50+5077G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001706.5(BCL6):​c.-50+5077G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,654 control chromosomes in the GnomAD database, including 21,901 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 (21901 hom., cov: 29)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 9 publications found

Genes affected

BCL6 (HGNC:1001): (BCL6 transcription repressor) The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001706.5. 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
	BCL6	NM_001706.5	MANE Select	c.-50+5077G>C		intron	N/A	NP_001697.2
	BCL6	NM_001134738.2		c.-50+5077G>C		intron	N/A	NP_001128210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.-50+5077G>C		intron	N/A	ENSP00000384371.2
	BCL6	ENST00000621333.4	TSL:5	c.-50+5077G>C		intron	N/A	ENSP00000479784.1
	BCL6	ENST00000470319.1	TSL:4	n.63+5077G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74436 AN: 151538 Hom.: 21899 Cov.: 29

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.491 AC: 74443 AN: 151654 Hom.: 21901 Cov.: 29 AF XY: 0.497 AC XY: 36842 AN XY: 74068

African (AFR) AF: 0.139 AC: 5755 AN: 41360

American (AMR) AF: 0.554 AC: 8446 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2365 AN: 3472

East Asian (EAS) AF: 0.590 AC: 3011 AN: 5102

South Asian (SAS) AF: 0.655 AC: 3130 AN: 4780

European-Finnish (FIN) AF: 0.653 AC: 6867 AN: 10512

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42839 AN: 67884

Other (OTH) AF: 0.540 AC: 1135 AN: 2102

Alfa AF: 0.542 Hom.: 3089

Bravo AF: 0.468

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.55
PhyloP100		-0.28
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1
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: rs3774303; hg19: chr3-187458121; COSMIC: COSV51649598;