ClinVar Genomic variation as it relates to human health
NM_004333.6(BRAF):c.1929A>G (p.Gly643=)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004333.6(BRAF):c.1929A>G (p.Gly643=)
Variation ID: 40391 Accession: VCV000040391.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q34 7: 140749350 (GRCh38) [ NCBI UCSC ] 7: 140449150 (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 Jan 16, 2015 Sep 29, 2024 Apr 18, 2017 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004333.6:c.1929A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004324.2:p.Gly643= synonymous NM_001374258.1:c.2049A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001361187.1:p.Gly683= synonymous NM_001354609.2:c.1929A>G NP_001341538.1:p.Gly643= synonymous NM_001374244.1:c.2049A>G NP_001361173.1:p.Gly683= synonymous NM_001378467.1:c.1938A>G NP_001365396.1:p.Gly646= synonymous NM_001378468.1:c.1929A>G NP_001365397.1:p.Gly643= synonymous NM_001378469.1:c.1863A>G NP_001365398.1:p.Gly621= synonymous NM_001378470.1:c.1827A>G NP_001365399.1:p.Gly609= synonymous NM_001378471.1:c.1818A>G NP_001365400.1:p.Gly606= synonymous NM_001378472.1:c.1773A>G NP_001365401.1:p.Gly591= synonymous NM_001378473.1:c.1773A>G NP_001365402.1:p.Gly591= synonymous NM_001378474.1:c.1929A>G NP_001365403.1:p.Gly643= synonymous NM_001378475.1:c.1665A>G NP_001365404.1:p.Gly555= synonymous NC_000007.14:g.140749350T>C NC_000007.13:g.140449150T>C NG_007873.3:g.180415A>G LRG_299:g.180415A>G LRG_299t1:c.1929A>G - Protein change
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- Other names
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p.G643G
p.G643G:GGA>GGG
NM_004333.4(BRAF):c.1929A>G
- Canonical SPDI
- NC_000007.14:140749349:T:C
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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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0.35104 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.20144
Exome Aggregation Consortium (ExAC) 0.21236
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.32001
1000 Genomes Project 0.35104
1000 Genomes Project 30x 0.35587
The Genome Aggregation Database (gnomAD) 0.30796
Trans-Omics for Precision Medicine (TOPMed) 0.31557
- Links
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 |
1256 | 1374 |
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 (4) |
reviewed by expert panel
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Apr 18, 2017 | RCV000033338.25 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
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Nov 16, 2017 | RCV000037940.31 | |
Benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV000306807.13 | |
Benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV000361471.13 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 29, 2023 | RCV000509253.22 | |
Benign (1) |
criteria provided, single submitter
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Dec 4, 2018 | RCV002408490.9 |
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
(Apr 18, 2017)
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reviewed by expert panel
Method: curation
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Noonan syndrome and Noonan-related syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen RASopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000616456.4 First in ClinVar: Dec 19, 2017 Last updated: Dec 11, 2022 |
Comment:
The filtering allele frequency of the c.1929A>G (p.Gly643=) variant in the BRAF gene is 66.117% (6984/10356) of African chromosomes by the Exome Aggregation Consortium, which … (more)
The filtering allele frequency of the c.1929A>G (p.Gly643=) variant in the BRAF gene is 66.117% (6984/10356) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) (less)
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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: SCV000310111.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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RASopathy
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001000055.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Benign
(Nov 29, 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: SCV001158928.8
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Jan 24, 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: SCV000057243.4
First in ClinVar: Jul 03, 2013 Last updated: May 27, 2015 |
Comment:
The variant is found in NOONAN panel(s).
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Benign
(May 19, 2015)
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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: SCV000058308.9
First in ClinVar: Apr 04, 2013 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 4
Zygosity: Single Heterozygote
Sex: mixed
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Benign
(Nov 16, 2017)
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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: SCV000918664.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: The BRAF c.1929A>G (p.Gly643Gly) variant involves the alteration of a nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism … (more)
Variant summary: The BRAF c.1929A>G (p.Gly643Gly) variant involves the alteration of a nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect any ESE site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 25661/120836 control chromosomes at a frequency of 0.2123622, which is approximately 84945 times the estimated maximal expected allele frequency of a pathogenic BRAF variant (0.0000025), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. (less)
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Benign
(Dec 03, 2007)
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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: SCV000061605.5
First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 1113
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Benign
(Jan 13, 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: SCV000466968.3
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 13, 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: SCV000466969.3
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
(Dec 04, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002720704.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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)
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Benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005270690.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Rasopathy
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV000196685.1
First in ClinVar: Jan 16, 2015 Last updated: Jan 16, 2015 |
Comment:
Variant classified using ACMG guidelines
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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: SCV000207628.1
First in ClinVar: Feb 19, 2015 Last updated: Feb 19, 2015 |
|
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not provided
(-)
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no classification provided
Method: phenotyping only
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Not Provided
Affected status: unknown
Allele origin:
unknown
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GenomeConnect, ClinGen
Accession: SCV000607337.1
First in ClinVar: Oct 16, 2017 Last updated: Oct 16, 2017 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Prenatal maternal abnormality (present) , Abnormal delivery (present) , Abnormality of the skull (present) , Abnormality of the nose (present) , Abnormality of the neck … (more)
Prenatal maternal abnormality (present) , Abnormal delivery (present) , Abnormality of the skull (present) , Abnormality of the nose (present) , Abnormality of the neck (present) , Abnormality of the oral cavity (present) , Abnormality of the hair (present) , Hearing impairment (present) , Aplasia/Hypoplasia of the ear (present) , Short attention span (present) , Generalized abnormality of skin (present) , Joint hypermobility (present) , Abnormality of the large intestine (present) , Abnormality of esophagus morphology (present) (less)
Age: 0-9 years
Sex: male
Testing laboratory: PreventionGenetics,PreventionGenetics
Date variant was reported to submitter: 2014-10-27
Testing laboratory interpretation: Benign
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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 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/043632b0-38d9-48f7-b0b4-993f0aa553b4 | - | - | - | - |
Text-mined citations for rs9648696 ...
HelpRecord last updated Nov 25, 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.