1-147552120-C-T

Variant names:

• chr1-147552120-C-T
• rs10494251
• NM_004326.4:c.-478+10446C>T

Variant summary

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

The NM_004326.4(BCL9):​c.-478+10446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 151,854 control chromosomes in the GnomAD database, including 423 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 0.061 (423 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-478+10446C>T		intron_variant	Intron 1 of 9	ENST00000234739.8	NP_004317.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL9	ENST00000234739.8	c.-478+10446C>T		intron_variant	Intron 1 of 9	1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.-478+10446C>T		intron_variant	Intron 1 of 9			ENSP00000506908.1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9262 AN: 151736 Hom.: 424 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0610 AC: 9259 AN: 151854 Hom.: 423 Cov.: 32 AF XY: 0.0625 AC XY: 4639 AN XY: 74192

African (AFR) AF: 0.0352 AC: 1456 AN: 41382

American (AMR) AF: 0.0928 AC: 1416 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1275 AN: 5136

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4824

European-Finnish (FIN) AF: 0.0501 AC: 527 AN: 10522

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0614 AC: 4172 AN: 67952

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0603 Hom.: 962

Bravo AF: 0.0639

Asia WGS AF: 0.112 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-0.14
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: rs10494251; hg19: chr1-147023894;