chr1-147614507-C-G

Variant names:

• chr1-147614507-C-G
• rs1178128117
• NM_004326.4:c.451C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004326.4(BCL9):​c.451C>G​(p.Pro151Ala) 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. 14/22 in silico tools predict a benign outcome for this variant. 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. P151R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCL9 NM_004326.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

Genes affected

BCL9 (HGNC:1008): (BCL9 transcription coactivator) BCL9 is associated with B-cell acute lymphoblastic leukemia. It may be a target of translocation in B-cell malignancies with abnormalities of 1q21. Its function is unknown. The overexpression of BCL9 may be of pathogenic significance in B-cell malignancies. [provided by RefSeq, Jul 2008]

BCL9 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19052407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004326.4. 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
	BCL9	NM_004326.4	MANE Select	c.451C>G	p.Pro151Ala	missense	Exon 6 of 10	NP_004317.2	O00512

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9	ENST00000234739.8	TSL:1 MANE Select	c.451C>G	p.Pro151Ala	missense	Exon 6 of 10	ENSP00000234739.3	O00512
	BCL9	ENST00000683836.1		c.451C>G	p.Pro151Ala	missense	Exon 6 of 10	ENSP00000506908.1	A0A804HI55
	BCL9	ENST00000684121.1		c.229C>G	p.Pro77Ala	missense	Exon 4 of 8	ENSP00000507238.1	A0A804HIV1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.067
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.18
Sift	Benign	0.18	T
Sift4G	Benign	0.097	T
Polyphen		0.77	P
Vest4		0.29
MutPred		0.15		Loss of glycosylation at P151 (P = 0.0283)
MVP		0.22
MPC		0.39
ClinPred		0.50	T
GERP RS		5.5
Varity_R		0.039
gMVP		0.17
Mutation Taster		=92/8	polymorphism

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: rs1178128117; hg19: chr1-147086306;