1-85276329-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003921.5(BCL10):c.24C>G(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,613,778 control chromosomes in the GnomAD database, including 71,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6012 hom., cov: 34)

Exomes 𝑓: 0.30 ( 65901 hom. )

Consequence

BCL10
NM_003921.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.122

Variant links:

Genes affected

BCL10 (HGNC:989): (BCL10 immune signaling adaptor) This gene was identified by its translocation in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. The protein encoded by this gene contains a caspase recruitment domain (CARD), and has been shown to induce apoptosis and to activate NF-kappaB. This protein is reported to interact with other CARD domain containing proteins including CARD9, 10, 11 and 14, which are thought to function as upstream regulators in NF-kappaB signaling. This protein is found to form a complex with MALT1, a protein encoded by another gene known to be translocated in MALT lymphoma. MALT1 and this protein are thought to synergize in the activation of NF-kappaB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

BCL10 links:

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

BCL10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-85276329-G-C is Benign according to our data. Variant chr1-85276329-G-C is described in ClinVar as [Benign]. Clinvar id is 402411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-85276329-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.122 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL10	NM_003921.5 link	c.24C>G	p.Leu8Leu	synonymous_variant	Exon 1 of 3	ENST00000648566.1	NP_003912.1	O95999

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL10	ENST00000648566.1 link	c.24C>G	p.Leu8Leu	synonymous_variant	Exon 1 of 3		NM_003921.5	ENSP00000498104.1		O95999

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

42027

AN:

152038

Hom.:

6009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.0749

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.271

AC:

67690

AN:

249826

Hom.:

9922

AF XY:

0.275

AC XY:

37196

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.0761

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.296

AC:

432591

AN:

1461622

Hom.:

65901

Cov.:

AF XY:

0.297

AC XY:

215760

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.0803

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.276

AC:

42055

AN:

152156

Hom.:

6012

Cov.:

AF XY:

0.274

AC XY:

20390

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.0750

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.310

Hom.:

2434

Bravo

AF:

0.270

Asia WGS

AF:

0.197

AC:

689

AN:

3478

EpiCase

AF:

0.311

EpiControl

AF:

0.314

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Associated with advanced germ cell tumors, unrelated to patient disease -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Immunodeficiency 37

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

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