1-147619150-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004326.4(BCL9):c.995C>T(p.Pro332Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0122 in 1,613,260 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (7 hom., cov: 32)
  • Exomes 𝑓: 0.013 (155 hom.)
• Consequence: BCL9 NM_004326.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.64

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028562248).
• BP6: Variant 1-147619150-C-T is Benign according to our data. Variant chr1-147619150-C-T is described in ClinVar as [Benign]. Clinvar id is 3024758.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-147619150-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL9	NM_004326.4	c.995C>T	p.Pro332Leu	missense_variant	8/10	ENST00000234739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9	ENST00000234739.8	c.995C>T	p.Pro332Leu	missense_variant	8/10	1	NM_004326.4	P2
BCL9	ENST00000683836.1	c.995C>T	p.Pro332Leu	missense_variant	8/10
BCL9	ENST00000684121.1	c.773C>T	p.Pro258Leu	missense_variant	6/8			A1

Frequencies

GnomAD3 genomes AF: 0.00909 AC: 1383 AN: 152186 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00872 AC: 2175 AN: 249564 Hom.: 14 AF XY: 0.00872 AC XY: 1178 AN XY: 135022

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.00360

Gnomad ASJ exome AF: 0.000303

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00263

Gnomad FIN exome AF: 0.0234

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00741

GnomAD4 exome AF: 0.0126 AC: 18378 AN: 1460956 Hom.: 155 Cov.: 31 AF XY: 0.0124 AC XY: 8993 AN XY: 726754

Gnomad4 AFR exome AF: 0.00185

Gnomad4 AMR exome AF: 0.00388

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00286

Gnomad4 FIN exome AF: 0.0226

Gnomad4 NFE exome AF: 0.0145

Gnomad4 OTH exome AF: 0.00976

GnomAD4 genome AF: 0.00909 AC: 1384 AN: 152304 Hom.: 7 Cov.: 32 AF XY: 0.00920 AC XY: 685 AN XY: 74470

Gnomad4 AFR AF: 0.00257

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0111 Hom.: 10

Bravo AF: 0.00714

TwinsUK AF: 0.0124 AC: 46

ALSPAC AF: 0.0145 AC: 56

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.00820 AC: 996

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0118

EpiControl AF: 0.00984

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

BCL9: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	20
Dann	Benign	0.75
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.82	D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.086
Sift	Benign	0.32	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.27
MVP		0.11
MPC		0.075
ClinPred		0.013	T
GERP RS		4.6
Varity_R		0.040
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs61751616; hg19: chr1-147090956;