3-187726422-T-C

Variant names:

• chr3-187726422-T-C
• rs1523475
• NM_001706.5:c.1708+309A>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.1708+309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,214 control chromosomes in the GnomAD database, including 43,908 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 0.75 (43908 hom., cov: 33)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 15 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]

ENSG00000228804 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1708+309A>G		intron_variant	Intron 7 of 9	ENST00000406870.7	NP_001697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.1708+309A>G		intron_variant	Intron 7 of 9	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114398 AN: 152096 Hom.: 43885 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.752 AC: 114467 AN: 152214 Hom.: 43908 Cov.: 33 AF XY: 0.755 AC XY: 56197 AN XY: 74420

African (AFR) AF: 0.590 AC: 24467 AN: 41500

American (AMR) AF: 0.854 AC: 13069 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2982 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4513 AN: 5174

South Asian (SAS) AF: 0.748 AC: 3607 AN: 4820

European-Finnish (FIN) AF: 0.798 AC: 8456 AN: 10602

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54639 AN: 68026

Other (OTH) AF: 0.788 AC: 1668 AN: 2116

Alfa AF: 0.800 Hom.: 96004

Bravo AF: 0.751

Asia WGS AF: 0.782 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.46
PhyloP100		0.021
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: rs1523475; hg19: chr3-187444210;