ClinVar Miner

Submissions for variant NM_001354689.3(RAF1):c.-267G>A (rs116247741)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV001030073 SCV001192861 benign Rasopathy 2019-07-25 reviewed by expert panel curation The c.-267G>A variant was identified in the RAF1 gene. The filtering allele frequency for the c.-267G>A is 6.32% for African chromosomes in gnomAD (68/8706 with 95% CI) (https://gnomad.broadinstitute.org/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). The variant has also been identified in a patient with an alternate molecular basis for disease (BP5; Laboratory for Molecular Medicine internal data). In summary, the c.-267G>A variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BA1, BP5.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154580 SCV000204253 likely benign not specified 2011-11-17 criteria provided, single submitter clinical testing This variant is located in the 5'UTR and variants in regulatory regions could ha ve an effect on transcriptional or translational efficiency. However, variants o f this type have not been reported in Noonan spectrum disorders to date. In addi tion, this variant has now been identified in 2/58 (3.4%) Black probands tested by our laboratory, including one proband with a pathogenic PTPN11 variant. This variant may be common in the Black population and therefore unlikely to be patho genic.
Illumina Clinical Services Laboratory,Illumina RCV000291471 SCV000440653 likely benign Noonan syndrome 5 2018-01-13 criteria provided, single submitter clinical testing 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.
Illumina Clinical Services Laboratory,Illumina RCV000344111 SCV000440654 benign LEOPARD syndrome 2 2018-01-13 criteria provided, single submitter clinical testing 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.