NM_004326.4:c.-477-7578T>G

Variant names:

• chr1-147597199-T-G
• rs2353525
• NM_004326.4:c.-477-7578T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004326.4(BCL9):​c.-477-7578T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,070 control chromosomes in the GnomAD database, including 14,272 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 0.34 (14272 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9	NM_004326.4	MANE Select	c.-477-7578T>G		intron	N/A	NP_004317.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9	ENST00000234739.8	TSL:1 MANE Select	c.-477-7578T>G		intron	N/A	ENSP00000234739.3
	BCL9	ENST00000683836.1		c.-477-7578T>G		intron	N/A	ENSP00000506908.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51080 AN: 151950 Hom.: 14228 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.337 AC: 51179 AN: 152070 Hom.: 14272 Cov.: 32 AF XY: 0.335 AC XY: 24887 AN XY: 74368

African (AFR) AF: 0.757 AC: 31396 AN: 41452

American (AMR) AF: 0.336 AC: 5135 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1859 AN: 5174

South Asian (SAS) AF: 0.241 AC: 1165 AN: 4828

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10582

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8740 AN: 67982

Other (OTH) AF: 0.291 AC: 614 AN: 2108

Alfa AF: 0.254 Hom.: 1105

Bravo AF: 0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0090
PhyloP100		-3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2353525; hg19: chr1-147068992;