rs946903

chr1-147625465-T-C

Variant summary

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

The NM_004326.4(BCL9):c.*506T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 225,736 control chromosomes in the GnomAD database, including 7,923 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 0.25 (5767 hom., cov: 30)
  • Exomes 𝑓: 0.22 (2156 hom.)
• Consequence: BCL9 NM_004326.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL9	NM_004326.4	c.*506T>C		3_prime_UTR_variant	10/10	ENST00000234739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9	ENST00000234739.8	c.*506T>C		3_prime_UTR_variant	10/10	1	NM_004326.4	P2
BCL9	ENST00000683836.1	c.*506T>C		3_prime_UTR_variant	10/10
BCL9	ENST00000684121.1	c.*506T>C		3_prime_UTR_variant	8/8			A1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38308 AN: 151500 Hom.: 5759 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0874

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.222 AC: 16481 AN: 74118 Hom.: 2156 Cov.: 0 AF XY: 0.222 AC XY: 7612 AN XY: 34362

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.253 AC: 38342 AN: 151618 Hom.: 5767 Cov.: 30 AF XY: 0.248 AC XY: 18363 AN XY: 74068

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.248

Alfa AF: 0.201 Hom.: 3370

Bravo AF: 0.279

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	15
Dann	Benign	0.82

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: rs946903; hg19: chr1-147097266;