17-7024535-A-G

Variant names:

• chr17-7024535-A-G
• NM_181844.4:c.536A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181844.4(BCL6B):​c.536A>G​(p.Gln179Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BCL6B NM_181844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

BCL6B (HGNC:1002): (BCL6B transcription repressor) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including regulation of gene expression; regulation of inflammatory response; and type 2 immune response. Predicted to be located in nucleus. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11380327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6B	NM_181844.4	c.536A>G	p.Gln179Arg	missense_variant	Exon 4 of 9	ENST00000293805.10	NP_862827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6B	ENST00000293805.10	c.536A>G	p.Gln179Arg	missense_variant	Exon 4 of 9	1	NM_181844.4	ENSP00000293805.5
BCL6B	ENST00000572216.1	n.444A>G		non_coding_transcript_exon_variant	Exon 4 of 4	4
BCL6B	ENST00000576705.1	c.*231A>G		downstream_gene_variant		4		ENSP00000460071.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.536A>G (p.Q179R) alteration is located in exon 4 (coding exon 3) of the BCL6B gene. This alteration results from a A to G substitution at nucleotide position 536, causing the glutamine (Q) at amino acid position 179 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.041
Sift	Benign	0.77	T
Sift4G	Benign	0.53	T
Polyphen		0.0070	B
Vest4		0.36
MutPred		0.23		Gain of methylation at Q179 (P = 0.0883);
MVP		0.51
MPC		0.60
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-6927854;