rs688325

Positions:

• chr1-147605490-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004326.4(BCL9):​c.-343+579G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,104 control chromosomes in the GnomAD database, including 3,715 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 0.20 (3715 hom., cov: 33)
• Consequence: BCL9 NM_004326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL9	NM_004326.4	c.-343+579G>A		intron_variant		ENST00000234739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9	ENST00000234739.8	c.-343+579G>A		intron_variant		1	NM_004326.4	P2
BCL9	ENST00000683836.1	c.-343+579G>A		intron_variant
BCL9	ENST00000497938.1	n.277+579G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29728 AN: 151984 Hom.: 3711 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.196 AC: 29763 AN: 152104 Hom.: 3715 Cov.: 33 AF XY: 0.200 AC XY: 14841 AN XY: 74354

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.198

Alfa AF: 0.148 Hom.: 1953

Bravo AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs688325; hg19: chr1-147077283;