NM_001706.5:c.-50+4110A>C

Variant names:

• chr3-187741300-T-G
• rs3172469
• NM_001706.5:c.-50+4110A>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+4110A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,062 control chromosomes in the GnomAD database, including 8,525 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 0.32 (8525 hom., cov: 32)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 13 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 (AFR) allele frequency at 95% confidence interval = 0.457 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+4110A>C		intron	N/A	NP_001697.2
	BCL6	NM_001134738.2		c.-50+4110A>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+4110A>C		intron	N/A	ENSP00000384371.2
	BCL6	ENST00000621333.4	TSL:5	c.-50+4110A>C		intron	N/A	ENSP00000479784.1
	BCL6	ENST00000470319.1	TSL:4	n.63+4110A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48754 AN: 151944 Hom.: 8513 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.321 AC: 48803 AN: 152062 Hom.: 8525 Cov.: 32 AF XY: 0.318 AC XY: 23647 AN XY: 74334

African (AFR) AF: 0.463 AC: 19169 AN: 41440

American (AMR) AF: 0.215 AC: 3286 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1944 AN: 5172

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4816

European-Finnish (FIN) AF: 0.309 AC: 3271 AN: 10576

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18592 AN: 67986

Other (OTH) AF: 0.283 AC: 596 AN: 2106

Alfa AF: 0.267 Hom.: 10598

Bravo AF: 0.321

Asia WGS AF: 0.320 AC: 1110 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	2.8
DANN	Benign	0.55
PhyloP100		-0.23
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: rs3172469; hg19: chr3-187459088;