3-187736943-C-G

Variant names:

• chr3-187736943-C-G
• rs3774304
• NM_001706.5:c.-49-2036G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001706.5(BCL6):​c.-49-2036G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,114 control chromosomes in the GnomAD database, including 21,991 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 0.49 (21984 hom., cov: 31)
  • Exomes 𝑓: 0.56 (7 hom.)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.-49-2036G>C		intron_variant	Intron 1 of 9	ENST00000406870.7	NP_001697.2
BCL6	XM_005247694.5	c.-50+654G>C		intron_variant	Intron 1 of 9		XP_005247751.1
BCL6	XM_047448655.1	c.-49-2036G>C		intron_variant	Intron 1 of 9		XP_047304611.1
BCL6	XM_011513062.4	c.-49-2036G>C		intron_variant	Intron 1 of 8		XP_011511364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.-49-2036G>C		intron_variant	Intron 1 of 9	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75033 AN: 151944 Hom.: 21978 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.560 AC: 28 AN: 50 Hom.: 7 Cov.: 0 AF XY: 0.625 AC XY: 15 AN XY: 24

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.600

GnomAD4 genome AF: 0.494 AC: 75061 AN: 152064 Hom.: 21984 Cov.: 31 AF XY: 0.501 AC XY: 37269 AN XY: 74322

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.546

Alfa AF: 0.386 Hom.: 1181

Bravo AF: 0.476

Asia WGS AF: 0.601 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.2
DANN	Benign	0.66

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: rs3774304; hg19: chr3-187454731; COSMIC: COSV51649578; COSMIC: COSV51649578;