chr1-147581540-G-A

Variant names:

• chr1-147581540-G-A
• rs672607
• NM_004326.4:c.-477-23237G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004326.4(BCL9):​c.-477-23237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,184 control chromosomes in the GnomAD database, including 2,005 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 0.12 (2005 hom., cov: 32)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9	NM_004326.4	c.-477-23237G>A		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.-477-23237G>A		intron_variant	Intron 1 of 9	1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.-477-23237G>A		intron_variant	Intron 1 of 9			ENSP00000506908.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18585 AN: 152066 Hom.: 1996 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.122 AC: 18622 AN: 152184 Hom.: 2005 Cov.: 32 AF XY: 0.123 AC XY: 9124 AN XY: 74416

African (AFR) AF: 0.240 AC: 9969 AN: 41480

American (AMR) AF: 0.215 AC: 3284 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1561 AN: 5174

South Asian (SAS) AF: 0.113 AC: 548 AN: 4830

European-Finnish (FIN) AF: 0.0364 AC: 387 AN: 10622

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2408 AN: 68012

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.0880 Hom.: 152

Bravo AF: 0.144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs672607; hg19: chr1-147053340;