rs594206

Positions:

• chr1-147548685-A-G

Variant summary

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

The NM_004326.4(BCL9):​c.-478+7011A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,068 control chromosomes in the GnomAD database, including 3,852 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 0.22 (3852 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-478+7011A>G		intron_variant		ENST00000234739.8	NP_004317.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL9	ENST00000234739.8	c.-478+7011A>G		intron_variant		1	NM_004326.4	ENSP00000234739	P2
BCL9	ENST00000683836.1	c.-478+7011A>G		intron_variant				ENSP00000506908

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33305 AN: 151950 Hom.: 3852 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.219 AC: 33304 AN: 152068 Hom.: 3852 Cov.: 32 AF XY: 0.215 AC XY: 16010 AN XY: 74368

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0718

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.231

Alfa AF: 0.206 Hom.: 5329

Bravo AF: 0.225

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs594206; hg19: chr1-147020456;