chr3-187741709-T-C

Position:

• chr3-187741709-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

BCL6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL6	NM_001706.5	c.-50+3701A>G		intron_variant		ENST00000406870.7	NP_001697.2
BCL6	XM_047448655.1	c.-50+2194A>G		intron_variant			XP_047304611.1
BCL6	XM_011513062.4	c.-50+3701A>G		intron_variant			XP_011511364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.-50+3701A>G		intron_variant		1	NM_001706.5	ENSP00000384371.2

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

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.588

Alfa AF: 0.557 Hom.: 6156

Bravo AF: 0.514

Asia WGS AF: 0.557 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.72
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1523474; hg19: chr3-187459497; COSMIC: COSV69201744; COSMIC: COSV69201744;