chr1-147552120-C-T

Position:

• chr1-147552120-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• 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/exons	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-478+10446C>T		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+10446C>T		intron_variant		1	NM_004326.4	ENSP00000234739	P2
BCL9	ENST00000683836.1	c.-478+10446C>T		intron_variant				ENSP00000506908

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

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0584 Hom.: 373

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

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: rs10494251; hg19: chr1-147023894;