Variant 1-147618808-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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.

BS2

High Homozygotes in GnomAdExome4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9	NM_004326.4 linkuse as main transcript	c.661-8G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000234739.8	NP_004317.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
BCL9	ENST00000234739.8 linkuse as main transcript	c.661-8G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_004326.4	ENSP00000234739	P2
BCL9	ENST00000683836.1 linkuse as main transcript	c.661-8G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000506908
BCL9	ENST00000684121.1 linkuse as main transcript	c.439-8G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000507238	A1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

151944

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00183

AC XY:

172

AN XY:

93792

show subpopulations

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.:

Cov.:

AF XY:

0.00389

AC XY:

2600

AN XY:

667924

show subpopulations

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.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74324

show subpopulations

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.:

Bravo

AF:

0.00198

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over