1-147618808-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_004326.4(BCL9):c.661-8G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,513,868 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (20 hom.)
• Consequence: BCL9 NM_004326.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002803
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.32

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=-0.85).
• BP6: Variant 1-147618808-G-T is Benign according to our data. Variant chr1-147618808-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 718807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL9	NM_004326.4	c.661-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000234739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9	ENST00000234739.8	c.661-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004326.4	P2
BCL9	ENST00000683836.1	c.661-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
BCL9	ENST00000684121.1	c.439-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.00211 AC: 321 AN: 151944 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000992

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00397

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00170 AC: 302 AN: 177400 Hom.: 0 AF XY: 0.00183 AC XY: 172 AN XY: 93792

Gnomad AFR exome AF: 0.000659

Gnomad AMR exome AF: 0.000148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000466

Gnomad FIN exome AF: 0.000406

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00324

GnomAD4 exome AF: 0.00399 AC: 5430 AN: 1361806 Hom.: 20 Cov.: 30 AF XY: 0.00389 AC XY: 2600 AN XY: 667924

Gnomad4 AFR exome AF: 0.000332

Gnomad4 AMR exome AF: 0.000210

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000402

Gnomad4 FIN exome AF: 0.000722

Gnomad4 NFE exome AF: 0.00490

Gnomad4 OTH exome AF: 0.00241

GnomAD4 genome AF: 0.00211 AC: 321 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74324

Gnomad4 AFR AF: 0.000989

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00397

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00188 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 20, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	BCL9: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.034
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.052
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201382423; hg19: chr1-147090614;