1-147579693-C-T

Variant names:

• chr1-147579693-C-T
• rs1541187
• NM_004326.4:c.-477-25084C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 rank	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-477-25084C>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.-477-25084C>T		intron_variant	Intron 1 of 9	1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.-477-25084C>T		intron_variant	Intron 1 of 9			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

African (AFR) AF: 0.0664 AC: 2759 AN: 41520

American (AMR) AF: 0.283 AC: 4324 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3468

East Asian (EAS) AF: 0.0764 AC: 396 AN: 5182

South Asian (SAS) AF: 0.202 AC: 975 AN: 4816

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10554

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13850 AN: 67984

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.183 Hom.: 1728

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
PhyloP100		1.2
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: rs1541187; hg19: chr1-147051493;