ClinVar Genomic variation as it relates to human health
NM_004333.6(BRAF):c.-19C>T
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
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NM_004333.6(BRAF):c.-19C>T
Variation ID: 41445 Accession: VCV000041445.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q34 7: 140924722 (GRCh38) [ NCBI UCSC ] 7: 140624522 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 19, 2015 Feb 20, 2024 Jan 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004333.6:c.-19C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
5 prime UTR NM_001374258.1:c.-19C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
5 prime UTR NM_001354609.2:c.-19C>T 5 prime UTR NM_001374244.1:c.-19C>T 5 prime UTR NM_001378467.1:c.-19C>T 5 prime UTR NM_001378468.1:c.-19C>T 5 prime UTR NM_001378469.1:c.-19C>T 5 prime UTR NM_001378470.1:c.-19C>T 5 prime UTR NM_001378471.1:c.-19C>T 5 prime UTR NM_001378474.1:c.-19C>T 5 prime UTR NM_001378475.1:c.-19C>T 5 prime UTR NC_000007.14:g.140924722G>A NC_000007.13:g.140624522G>A NG_007873.3:g.5043C>T LRG_299:g.5043C>T LRG_299t1:c.-19C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000007.14:140924721:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.01538 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00029
The Genome Aggregation Database (gnomAD), exomes 0.00114
The Genome Aggregation Database (gnomAD) 0.01115
Trans-Omics for Precision Medicine (TOPMed) 0.01200
1000 Genomes Project 30x 0.01530
1000 Genomes Project 0.01538
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 | ||
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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. |
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BRAF | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1244 | 1358 |
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. |
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Benign (1) |
criteria provided, single submitter
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Mar 2, 2012 | RCV000034331.14 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Nov 25, 2019 | RCV000077864.29 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV000370547.13 | |
Benign (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV000406169.13 | |
Benign (1) |
criteria provided, single submitter
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Jan 3, 2023 | RCV001811235.16 |
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. |
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Benign
(Jan 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002048608.4
First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024 |
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000310103.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Mar 18, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000058304.9
First in ClinVar: Apr 04, 2013 Last updated: May 03, 2018 |
Number of individuals with the variant: 5
Sex: mixed
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Benign
(Nov 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001363012.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BRAF c.-19C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of … (more)
Variant summary: BRAF c.-19C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.0011 in 86066 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 455-folds over the estimated maximal expected allele frequency for a pathogenic variant in BRAF causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. Two ClinVar submissions (evaluation after 2014) cites the variant once as likely benign and once as benign. Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(Mar 02, 2012)
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criteria provided, single submitter
Method: clinical testing
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Rasopathy
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000077235.2
First in ClinVar: Jul 03, 2013 Last updated: Feb 24, 2015 |
Comment:
The variant is found in NOONAN panel(s).
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Likely benign
(Jun 01, 2011)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000197183.4
First in ClinVar: Jan 30, 2015 Last updated: Oct 02, 2016 |
Comment:
-19C>T in the 5'UTR of BRAF: This variant has been reported in dbSNP in 2.3% (1/ 44) Hispanic chromosomes and 4.2% (1/24) Black chromosomes (rs71645935). … (more)
-19C>T in the 5'UTR of BRAF: This variant has been reported in dbSNP in 2.3% (1/ 44) Hispanic chromosomes and 4.2% (1/24) Black chromosomes (rs71645935). This va riant is located in the 5'UTR and variants in regulatory regions could have an e ffect on transcriptional or translational efficiency. However, no variants in th is region of BRAF have been found to be pathogenic in individuals with Noonan sp ectrum disorders.Therefore, this variant is not expected to have clinical signif icance. (less)
Number of individuals with the variant: 4
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Likely benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 7
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000467009.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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LEOPARD syndrome 3
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000467007.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Jan 15, 2015)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV000207625.1
First in ClinVar: Feb 19, 2015 Last updated: Feb 19, 2015 |
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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 |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRAF | - | - | - | - |
Text-mined citations for rs71645935 ...
HelpRecord last updated Oct 08, 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.