rs1056932

Variant names:

• chr3-187729244-G-A
• rs1056932
• NM_001706.5:c.1161C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-187729244-G-A
• chr3-187729244-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001706.5(BCL6):​c.1161C>T​(p.Asn387Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,613,920 control chromosomes in the GnomAD database, including 341,613 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 0.54 (25905 hom., cov: 31)
  • Exomes 𝑓: 0.65 (315708 hom.)
• Consequence: BCL6 NM_001706.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 40 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.773 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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.1161C>T	p.Asn387Asn	synonymous	Exon 5 of 10	NP_001697.2
	BCL6	NM_001130845.2		c.1161C>T	p.Asn387Asn	synonymous	Exon 5 of 10	NP_001124317.1	P41182-1
	BCL6	NM_001134738.2		c.1161C>T	p.Asn387Asn	synonymous	Exon 5 of 9	NP_001128210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.1161C>T	p.Asn387Asn	synonymous	Exon 5 of 10	ENSP00000384371.2	P41182-1
	BCL6	ENST00000232014.8	TSL:1	c.1161C>T	p.Asn387Asn	synonymous	Exon 5 of 10	ENSP00000232014.4	P41182-1
	BCL6	ENST00000450123.6	TSL:1	c.1161C>T	p.Asn387Asn	synonymous	Exon 4 of 8	ENSP00000413122.2	P41182-2

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81937 AN: 151936 Hom.: 25893 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.596

GnomAD2 exomes AF: 0.658 AC: 165326 AN: 251440 AF XY: 0.661

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.776

Gnomad ASJ exome AF: 0.702

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.651 AC: 951884 AN: 1461866 Hom.: 315708 Cov.: 88 AF XY: 0.652 AC XY: 474009 AN XY: 727232

African (AFR) AF: 0.160 AC: 5344 AN: 33480

American (AMR) AF: 0.769 AC: 34409 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 18360 AN: 26136

East Asian (EAS) AF: 0.824 AC: 32727 AN: 39700

South Asian (SAS) AF: 0.646 AC: 55701 AN: 86258

European-Finnish (FIN) AF: 0.690 AC: 36830 AN: 53404

Middle Eastern (MID) AF: 0.694 AC: 4004 AN: 5766

European-Non Finnish (NFE) AF: 0.652 AC: 725547 AN: 1112002

Other (OTH) AF: 0.645 AC: 38962 AN: 60396

GnomAD4 genome AF: 0.539 AC: 81972 AN: 152054 Hom.: 25905 Cov.: 31 AF XY: 0.549 AC XY: 40771 AN XY: 74304

African (AFR) AF: 0.184 AC: 7637 AN: 41524

American (AMR) AF: 0.702 AC: 10734 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2462 AN: 3468

East Asian (EAS) AF: 0.799 AC: 4103 AN: 5134

South Asian (SAS) AF: 0.655 AC: 3143 AN: 4796

European-Finnish (FIN) AF: 0.701 AC: 7417 AN: 10574

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44272 AN: 67942

Other (OTH) AF: 0.597 AC: 1260 AN: 2110

Alfa AF: 0.616 Hom.: 50120

Bravo AF: 0.525

Asia WGS AF: 0.669 AC: 2327 AN: 3478

EpiCase AF: 0.666

EpiControl AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.9
DANN	Benign	0.84
PhyloP100		0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	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: rs1056932; hg19: chr3-187447032; COSMIC: COSV51649553; COSMIC: COSV51649553;