ClinVar Genomic variation as it relates to human health
NM_002880.4(RAF1):c.1941C>T (p.Val647=)
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_002880.4(RAF1):c.1941C>T (p.Val647=)
Variation ID: 44623 Accession: VCV000044623.41
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.2 3: 12584520 (GRCh38) [ NCBI UCSC ] 3: 12626019 (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 17, 2015 May 12, 2024 Apr 18, 2017 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002880.4:c.1941C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002871.1:p.Val647= synonymous NM_001354689.3:c.2001C>T NP_001341618.1:p.Val667= synonymous NM_001354690.3:c.1941C>T NP_001341619.1:p.Val647= synonymous NM_001354691.3:c.1698C>T NP_001341620.1:p.Val566= synonymous NM_001354692.3:c.1698C>T NP_001341621.1:p.Val566= synonymous NM_001354693.3:c.1842C>T NP_001341622.1:p.Val614= synonymous NM_001354694.3:c.1758C>T NP_001341623.1:p.Val586= synonymous NM_001354695.3:c.1599C>T NP_001341624.1:p.Val533= synonymous NR_148940.3:n.2385C>T non-coding transcript variant NR_148941.3:n.2331C>T non-coding transcript variant NR_148942.3:n.2270C>T non-coding transcript variant NC_000003.12:g.12584520G>A NC_000003.11:g.12626019G>A NG_007467.1:g.84660C>T LRG_413:g.84660C>T LRG_413t1:c.1941C>T LRG_413p1:p.Val647= LRG_413t2:c.2001C>T LRG_413p2:p.Val667= - Protein change
- Other names
- p.V647V:GTC>GTT
- NM_002880.3(RAF1):c.1941C>T
- Canonical SPDI
- NC_000003.12:12584519: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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0.00439 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00439
1000 Genomes Project 30x 0.00468
Trans-Omics for Precision Medicine (TOPMed) 0.00652
The Genome Aggregation Database (gnomAD), exomes 0.00679
Exome Aggregation Consortium (ExAC) 0.00708
The Genome Aggregation Database (gnomAD) 0.00729
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00830
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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RAF1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
1070 | 1124 | |
MKRN2 | - | - |
GRCh38 GRCh37 |
28 | 61 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jan 12, 2012 | RCV000037685.18 | |
Benign (3) |
reviewed by expert panel
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Apr 18, 2017 | RCV000149840.25 | |
Benign (1) |
criteria provided, single submitter
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Dec 8, 2014 | RCV000252430.11 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000857577.23 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001143979.12 | |
Benign (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001145869.12 | |
Benign (1) |
criteria provided, single submitter
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Jul 8, 2021 | RCV001813331.11 |
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
|
ClinGen RASopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000616477.4 First in ClinVar: Dec 19, 2017 Last updated: Dec 11, 2022 |
Comment:
The filtering allele frequency of the c.1941C>T (p.Val647=) variant in the RAF1 gene is 1.04% (738/66732) of European chromosomes by the Exome Aggregation Consortium, which … (more)
The filtering allele frequency of the c.1941C>T (p.Val647=) variant in the RAF1 gene is 1.04% (738/66732) of European 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
(Jul 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome and Noonan-related syndrome
Affected status: unknown
Allele origin:
germline
|
Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002060609.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
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Benign
(Jan 12, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000171286.11
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
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)
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Benign
(May 11, 2009)
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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: SCV000061347.6
First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 68
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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 5
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001304553.1
First in ClinVar: May 31, 2020 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 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001306573.1
First in ClinVar: May 31, 2020 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
(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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Invitae
Accession: SCV000287741.10
First in ClinVar: Jul 01, 2016 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: SCV000309261.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Benign
(Nov 09, 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: SCV001472278.3
First in ClinVar: Jan 26, 2021 Last updated: Feb 20, 2024 |
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Benign
(Dec 08, 2014)
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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: SCV000318679.7
First in ClinVar: Oct 02, 2016 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
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV003916410.8
First in ClinVar: Apr 23, 2023 Last updated: May 12, 2024 |
Comment:
MKRN2: BS1, BS2; RAF1: BP4, BS1, BS2
Number of individuals with the variant: 18
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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: SCV000196684.1
First in ClinVar: Jan 17, 2015 Last updated: Jan 17, 2015 |
Comment:
Variant classified using ACMG guidelines
|
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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 - CFC International
Accession: SCV001156335.1
First in ClinVar: Feb 06, 2020 Last updated: Feb 06, 2020 |
Comment:
Variant interpreted as Benign and reported on 04-30-2009 by Lab or GTR ID 239772. GenomeConnect-CFC International assertions are reported exactly as they appear on the … (more)
Variant interpreted as Benign and reported on 04-30-2009 by Lab or GTR ID 239772. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of eye movement (present) , Hypermetropia (present) , Myopia (present) , Ptosis (present) , Abnormal facial shape (present) , Abnormality of the oral cavity … (more)
Abnormality of eye movement (present) , Hypermetropia (present) , Myopia (present) , Ptosis (present) , Abnormal facial shape (present) , Abnormality of the oral cavity (present) , Abnormality of the neck (present) , Abnormality of the nose (present) , Feeding difficulties (present) , Abnormality of the intestine (present) , Abnormality of the large intestine (present) , Abnormality of the stomach (present) , Abnormality of the bladder (present) , Abnormal renal physiology (present) , Abnormal renal morphology (present) , Abnormality of the male genitalia (present) , Abnormality of the urethra (present) , Abnormality of the ureter (present) , Abnormality of the curvature of the vertebral column (present) , Joint hypermobility (present) , Abnormality of the musculature of the limbs (present) , Abnormality of the musculature of the pelvis (present) , Abnormality of muscle morphology (present) , Abnormality of muscle physiology (present) , Morphological abnormality of the central nervous system (present) , Cerebral palsy (present) , Cognitive impairment (present) , Generalized hypotonia (present) , Seizures (present) , Abnormality of the amniotic fluid (present) , Abnormal delivery (present) , Premature birth (present) , Autistic behavior (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Testing laboratory: PreventionGenetics,PreventionGenetics
Date variant was reported to submitter: 2009-04-30
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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https://erepo.clinicalgenome.org/evrepo/ui/interpretation/62438d26-e85a-41a6-ae0f-89550c868512 | - | - | - | - |
Text-mined citations for rs3730297 ...
HelpRecord last updated May 19, 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.