1-147588715-T-C

Variant names:

• chr1-147588715-T-C
• rs11240089
• NM_004326.4:c.-477-16062T>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.-477-16062T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,040 control chromosomes in the GnomAD database, including 13,939 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 0.32 (13939 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-477-16062T>C		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.-477-16062T>C		intron_variant	Intron 1 of 9	1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.-477-16062T>C		intron_variant	Intron 1 of 9			ENSP00000506908.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49260 AN: 151922 Hom.: 13895 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.325 AC: 49359 AN: 152040 Hom.: 13939 Cov.: 32 AF XY: 0.323 AC XY: 24040 AN XY: 74336

African (AFR) AF: 0.754 AC: 31257 AN: 41436

American (AMR) AF: 0.327 AC: 5006 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1850 AN: 5150

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10594

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7416 AN: 67978

Other (OTH) AF: 0.282 AC: 595 AN: 2110

Alfa AF: 0.220 Hom.: 3846

Bravo AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
PhyloP100		-0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11240089; hg19: chr1-147060514;