chr17-7023708-T-G

Variant names:

• chr17-7023708-T-G
• rs1172599956
• NM_181844.4:c.37T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181844.4(BCL6B):​c.37T>G​(p.Tyr13Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y13H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: BCL6B NM_181844.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181844.4. 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
	BCL6B	NM_181844.4	MANE Select	c.37T>G	p.Tyr13Asp	missense	Exon 2 of 9	NP_862827.2	Q8N143

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6B	ENST00000293805.10	TSL:1 MANE Select	c.37T>G	p.Tyr13Asp	missense	Exon 2 of 9	ENSP00000293805.5	Q8N143
	BCL6B	ENST00000896967.1		c.37T>G	p.Tyr13Asp	missense	Exon 2 of 9	ENSP00000567026.1
	BCL6B	ENST00000896964.1		c.37T>G	p.Tyr13Asp	missense	Exon 2 of 9	ENSP00000567024.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.50		Gain of disorder (P = 0.0039)
MVP		0.89
MPC		1.6
ClinPred		0.94	D
GERP RS		5.8
PromoterAI		-0.064	Neutral
Varity_R		0.56
gMVP		0.89

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: rs1172599956; hg19: chr17-6927027;