rs369396168

Variant names:

• chr17-7024228-C-T
• rs369396168
• NM_181844.4:c.325C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7024228-C-T
• chr17-7024228-C-A
• chr17-7024228-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181844.4(BCL6B):​c.325C>T​(p.Pro109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P109R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (1 hom.)
• Consequence: BCL6B NM_181844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.179
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03830287).

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.325C>T	p.Pro109Ser	missense	Exon 3 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.325C>T	p.Pro109Ser	missense	Exon 3 of 9	ENSP00000293805.5	Q8N143
	BCL6B	ENST00000896967.1		c.325C>T	p.Pro109Ser	missense	Exon 3 of 9	ENSP00000567026.1
	BCL6B	ENST00000896964.1		c.325C>T	p.Pro109Ser	missense	Exon 3 of 9	ENSP00000567024.1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000723 AC: 18 AN: 249082 AF XY: 0.0000443

Gnomad AFR exome AF: 0.000777

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461576 Hom.: 1 Cov.: 39 AF XY: 0.0000179 AC XY: 13 AN XY: 727104

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74484

African (AFR) AF: 0.00103 AC: 43 AN: 41564

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000613 Hom.: 0

Bravo AF: 0.000336

ESP6500AA AF: 0.000243 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000661 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.050	N
PhyloP100		0.18
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.10
Sift	Benign	0.55	T
Sift4G	Uncertain	0.050	T
Polyphen		0.82	P
Vest4		0.12
MVP		0.84
MPC		0.85
ClinPred		0.031	T
GERP RS		5.2
Varity_R		0.074
gMVP		0.42
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369396168; hg19: chr17-6927547;