chr1-147548685-A-G

Variant names:

• chr1-147548685-A-G
• rs594206
• NM_004326.4:c.-478+7011A>G

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+7011A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,068 control chromosomes in the GnomAD database, including 3,852 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 0.22 (3852 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-478+7011A>G		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+7011A>G		intron_variant	Intron 1 of 9	1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.-478+7011A>G		intron_variant	Intron 1 of 9			ENSP00000506908.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33305 AN: 151950 Hom.: 3852 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.219 AC: 33304 AN: 152068 Hom.: 3852 Cov.: 32 AF XY: 0.215 AC XY: 16010 AN XY: 74368

African (AFR) AF: 0.293 AC: 12126 AN: 41420

American (AMR) AF: 0.202 AC: 3083 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3468

East Asian (EAS) AF: 0.0718 AC: 370 AN: 5154

South Asian (SAS) AF: 0.156 AC: 754 AN: 4828

European-Finnish (FIN) AF: 0.151 AC: 1596 AN: 10602

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13811 AN: 67986

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.208 Hom.: 12855

Bravo AF: 0.225

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.86
PhyloP100		0.066
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: rs594206; hg19: chr1-147020456;