rs672607

chr1-147581540-G-Achr1-147581540-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004326.4(BCL9):c.-477-23237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,184 control chromosomes in the GnomAD database, including 2,005 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 0.12 (2005 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL9	NM_004326.4	c.-477-23237G>A		intron_variant		ENST00000234739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9	ENST00000234739.8	c.-477-23237G>A		intron_variant		1	NM_004326.4	P2
BCL9	ENST00000683836.1	c.-477-23237G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18585 AN: 152066 Hom.: 1996 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.122 AC: 18622 AN: 152184 Hom.: 2005 Cov.: 32 AF XY: 0.123 AC XY: 9124 AN XY: 74416

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0364

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0880 Hom.: 152

Bravo AF: 0.144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs672607; hg19: chr1-147053340;