rs946903

Variant names:

• chr1-147625465-T-C
• rs946903
• NM_004326.4:c.*506T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9	NM_004326.4	MANE Select	c.*506T>C		3_prime_UTR	Exon 10 of 10	NP_004317.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9	ENST00000234739.8	TSL:1 MANE Select	c.*506T>C		3_prime_UTR	Exon 10 of 10	ENSP00000234739.3
	BCL9	ENST00000683836.1		c.*506T>C		3_prime_UTR	Exon 10 of 10	ENSP00000506908.1
	BCL9	ENST00000684121.1		c.*506T>C		3_prime_UTR	Exon 8 of 8	ENSP00000507238.1

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

African (AFR) AF: 0.424 AC: 1428 AN: 3370

American (AMR) AF: 0.338 AC: 770 AN: 2280

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 1101 AN: 4646

East Asian (EAS) AF: 0.349 AC: 3654 AN: 10476

South Asian (SAS) AF: 0.195 AC: 135 AN: 694

European-Finnish (FIN) AF: 0.116 AC: 56 AN: 484

Middle Eastern (MID) AF: 0.269 AC: 119 AN: 442

European-Non Finnish (NFE) AF: 0.173 AC: 7872 AN: 45622

Other (OTH) AF: 0.221 AC: 1346 AN: 6104

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

African (AFR) AF: 0.419 AC: 17263 AN: 41218

American (AMR) AF: 0.299 AC: 4551 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1445 AN: 5142

South Asian (SAS) AF: 0.194 AC: 931 AN: 4790

European-Finnish (FIN) AF: 0.0874 AC: 919 AN: 10520

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11645 AN: 67930

Other (OTH) AF: 0.248 AC: 523 AN: 2106

Alfa AF: 0.211 Hom.: 4930

Bravo AF: 0.279

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs946903; hg19: chr1-147097266;