3-187741709-T-C

Variant names:

• chr3-187741709-T-C
• rs1523474
• NM_001706.5:c.-50+3701A>G

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+3701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,082 control chromosomes in the GnomAD database, including 24,311 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 0.53 (24311 hom., cov: 32)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	NM_001706.5	MANE Select	c.-50+3701A>G		intron	N/A	NP_001697.2
	BCL6	NM_001134738.2		c.-50+3701A>G		intron	N/A	NP_001128210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.-50+3701A>G		intron	N/A	ENSP00000384371.2	P41182-1
	BCL6	ENST00000621333.4	TSL:5	c.-50+3701A>G		intron	N/A	ENSP00000479784.1	P41182-2
	BCL6	ENST00000470319.1	TSL:4	n.63+3701A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81129 AN: 151964 Hom.: 24305 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.534 AC: 81154 AN: 152082 Hom.: 24311 Cov.: 32 AF XY: 0.534 AC XY: 39680 AN XY: 74350

African (AFR) AF: 0.241 AC: 10008 AN: 41476

American (AMR) AF: 0.544 AC: 8308 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2917 AN: 5158

South Asian (SAS) AF: 0.684 AC: 3302 AN: 4824

European-Finnish (FIN) AF: 0.613 AC: 6485 AN: 10574

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45507 AN: 67976

Other (OTH) AF: 0.588 AC: 1243 AN: 2114

Alfa AF: 0.585 Hom.: 15260

Bravo AF: 0.514

Asia WGS AF: 0.557 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		0.65
RBP_binding_hub_radar		0.91
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: rs1523474; hg19: chr3-187459497; COSMIC: COSV69201744; COSMIC: COSV69201744;