3-187736943-C-G

Variant names:

• chr3-187736943-C-G
• rs3774304
• NM_001706.5:c.-49-2036G>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.-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
• Publications: 9 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 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.-49-2036G>C		intron	N/A	NP_001697.2
	BCL6	NM_001134738.2		c.-49-2036G>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.-49-2036G>C		intron	N/A	ENSP00000384371.2
	BCL6	ENST00000419510.6	TSL:2	n.-903G>C		non_coding_transcript_exon	Exon 1 of 10	ENSP00000398014.2
	BCL6	ENST00000496823.1	TSL:3	n.382G>C		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.600 AC: 24 AN: 40

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.153 AC: 6339 AN: 41482

American (AMR) AF: 0.577 AC: 8809 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2347 AN: 3470

East Asian (EAS) AF: 0.740 AC: 3822 AN: 5162

South Asian (SAS) AF: 0.623 AC: 3004 AN: 4820

European-Finnish (FIN) AF: 0.656 AC: 6927 AN: 10558

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.614 AC: 41770 AN: 67988

Other (OTH) AF: 0.546 AC: 1153 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.40
PromoterAI		0.0066	Neutral
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: rs3774304; hg19: chr3-187454731; COSMIC: COSV51649578;