1-147579693-C-T

Position:

• chr1-147579693-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004326.4(BCL9):​c.-477-25084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,122 control chromosomes in the GnomAD database, including 2,741 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 0.17 (2741 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-477-25084C>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.-477-25084C>T		intron_variant		1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.-477-25084C>T		intron_variant				ENSP00000506908.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25861 AN: 152004 Hom.: 2729 Cov.: 32

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.170 AC: 25883 AN: 152122 Hom.: 2741 Cov.: 32 AF XY: 0.171 AC XY: 12708 AN XY: 74360

Gnomad4 AFR AF: 0.0664

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.202

Alfa AF: 0.183 Hom.: 1571

Bravo AF: 0.176

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.83

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: rs1541187; hg19: chr1-147051493;