chr1-85270827-A-AT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_003921.5(BCL10):c.136dupA(p.Ile46AsnfsTer4) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BCL10
NM_003921.5 frameshift
NM_003921.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.35
Publications
11 publications found
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 Gene-Disease associations (from GenCC):
- immunodeficiency 37Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-85270827-A-AT is Pathogenic according to our data. Variant chr1-85270827-A-AT is described in ClinVar as Pathogenic. ClinVar VariationId is 6259.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003921.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BCL10 | NM_003921.5 | MANE Select | c.136dupA | p.Ile46AsnfsTer4 | frameshift | Exon 2 of 3 | NP_003912.1 | ||
| BCL10 | NM_001320715.2 | c.136dupA | p.Ile46AsnfsTer4 | frameshift | Exon 2 of 3 | NP_001307644.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BCL10 | ENST00000648566.1 | MANE Select | c.136dupA | p.Ile46AsnfsTer4 | frameshift | Exon 2 of 3 | ENSP00000498104.1 | ||
| BCL10 | ENST00000913809.1 | c.133dupA | p.Ile45AsnfsTer4 | frameshift | Exon 2 of 3 | ENSP00000583868.1 | |||
| BCL10 | ENST00000620248.3 | TSL:5 | c.136dupA | p.Ile46AsnfsTer4 | frameshift | Exon 2 of 3 | ENSP00000480561.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1459676Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726162
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1459676
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726162
African (AFR)
AF:
AC:
0
AN:
33436
American (AMR)
AF:
AC:
0
AN:
44518
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26100
East Asian (EAS)
AF:
AC:
0
AN:
39622
South Asian (SAS)
AF:
AC:
0
AN:
86080
European-Finnish (FIN)
AF:
AC:
0
AN:
53068
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1110772
Other (OTH)
AF:
AC:
0
AN:
60318
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Carcinoma of colon (1)
1
-
-
T-cell acute lymphoblastic leukemia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.