ClinVar Genomic variation as it relates to human health
NM_005188.4(CBL):c.107ACC[8] (p.His42dup)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_005188.4(CBL):c.107ACC[8] (p.His42dup)
Variation ID: 40400 Accession: VCV000040400.39
- Type and length
-
Microsatellite, 3 bp
- Location
-
Cytogenetic: 11q23.3 11: 119206522-119206523 (GRCh38) [ NCBI UCSC ] 11: 119077232-119077233 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 31, 2015 Apr 15, 2024 Feb 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_005188.4:c.107ACC[8] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005179.2:p.His42dup inframe insertion NM_005188.4:c.125_127dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_005188.2:c.125_127dupACC NM_005188.3:c.125_127dupACC NC_000011.10:g.119206524ACC[8] NC_000011.9:g.119077234ACC[8] NG_016808.1:g.5245ACC[8] LRG_608:g.5245ACC[8] - Protein change
- Other names
- p.His42_Leu43insHis
- Canonical SPDI
- NC_000011.10:119206522:CACCACCACCACCACCACCACC:CACCACCACCACCACCACCACCACC
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00559 (CACCACCACCACCACCACCACCACC)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
CBL | No evidence available | No evidence available |
GRCh38 GRCh37 |
1412 | 1556 | |
LOC130006895 | - | - | - | GRCh38 | - | 98 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 4, 2022 | RCV000038350.18 | |
Likely benign (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000278774.6 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000514229.14 | |
Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV001080766.8 | |
Benign (1) |
criteria provided, single submitter
|
Dec 8, 2020 | RCV001813226.4 | |
Benign (1) |
criteria provided, single submitter
|
Dec 5, 2021 | RCV002490443.1 | |
Benign (1) |
criteria provided, single submitter
|
May 17, 2019 | RCV003924883.1 | |
Benign (1) |
criteria provided, single submitter
|
Dec 20, 2021 | RCV002408491.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely benign
(May 11, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610592.1
First in ClinVar: Nov 06, 2017 Last updated: Nov 06, 2017 |
|
|
Likely benign
(Oct 31, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000062022.5
First in ClinVar: May 03, 2013 Last updated: Aug 31, 2017 |
Comment:
c.125_127dupACC in exon 1 of CBL: This variant is not expected to have clinical significance because it has been identified in 0.2% (13/6806) of European … (more)
c.125_127dupACC in exon 1 of CBL: This variant is not expected to have clinical significance because it has been identified in 0.2% (13/6806) of European Americ an and 0.8% (27/3260) of African American chromosomes by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs397507488). This variant is an in-frame duplication which adds an additional histidine residue (His) to a short repeat of 7 histidines. Additionally, the number of histidines is not co nserved across species. (less)
Number of individuals with the variant: 4
|
|
Benign
(Jan 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000593861.2
First in ClinVar: Aug 28, 2017 Last updated: Jan 29, 2022 |
|
|
Benign
(Dec 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile myelomonocytic leukemia
CBL-related disorder
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002803544.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
RASopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000288829.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004033171.5
First in ClinVar: Sep 16, 2023 Last updated: Apr 15, 2024 |
Comment:
CBL: BS1, BS2
Number of individuals with the variant: 3
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Noonan-Like Syndrome Disorder
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000367751.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
Likely benign
(May 19, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000224467.3
First in ClinVar: Jun 28, 2015 Last updated: Aug 31, 2015 |
Number of individuals with the variant: 2
Sex: mixed
|
|
Benign
(Mar 11, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000057252.8
First in ClinVar: Apr 04, 2013 Last updated: Sep 21, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Benign
(Dec 10, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362211.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: CBL c.125_127dupACC (p.His42dup) results in a in-frame duplication which adds an additional histidine residue to a short repeat of 7 histidines. The variant … (more)
Variant summary: CBL c.125_127dupACC (p.His42dup) results in a in-frame duplication which adds an additional histidine residue to a short repeat of 7 histidines. The variant allele was found at a frequency of 0.002 in 151840 control chromosomes, predominantly at a frequency of 0.011 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4400 fold of the estimated maximal expected allele frequency for a pathogenic variant in CBL causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. (less)
|
|
Benign
(Dec 08, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Noonan syndrome and Noonan-related syndrome
Affected status: unknown
Allele origin:
germline
|
Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002060486.1
First in ClinVar: Jan 20, 2022 Last updated: Jan 20, 2022 |
|
|
Benign
(Dec 20, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002674655.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
|
|
Benign
(May 17, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
CBL-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004742156.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001923137.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001797653.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy. | Spiegel JY | Blood advances | 2017 | PMID: 29296819 |
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. | Arber DA | Blood | 2016 | PMID: 27069254 |
TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. | Bejar R | Blood | 2014 | PMID: 25224413 |
Prognostic score including gene mutations in chronic myelomonocytic leukemia. | Itzykson R | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2013 | PMID: 23690417 |
Use of CBL exon 8 and 9 mutations in diagnosis of myeloproliferative neoplasms and myelodysplastic/myeloproliferative disorders: an analysis of 636 cases. | Schnittger S | Haematologica | 2012 | PMID: 22733026 |
Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. | Jankowska AM | Blood | 2011 | PMID: 21828135 |
Myeloid leukemia development in c-Cbl RING finger mutant mice is dependent on FLT3 signaling. | Rathinam C | Cancer cell | 2010 | PMID: 20951944 |
Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies. | Makishima H | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2009 | PMID: 19901108 |
Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. | Sanada M | Nature | 2009 | PMID: 19620960 |
Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. | Grand FH | Blood | 2009 | PMID: 19387008 |
Text-mined citations for rs373212940 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.