Submissions for variant NM_004333.6(BRAF):c.-19C>T

gnomAD frequency: 0.01115  dbSNP: rs71645935

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000077864	SCV000058304	benign	not specified	2013-03-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000034331	SCV000077235	benign	RASopathy	2012-03-02	criteria provided, single submitter	clinical testing	The variant is found in NOONAN panel(s).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000077864	SCV000197183	likely benign	not specified	2011-06-01	criteria provided, single submitter	clinical testing	-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.
PreventionGenetics, part of Exact Sciences	RCV000077864	SCV000310103	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406169	SCV000467007	benign	LEOPARD syndrome 3	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV000370547	SCV000467009	likely benign	Noonan syndrome 7	2018-01-12	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000077864	SCV001363012	benign	not specified	2019-11-25	criteria provided, single submitter	clinical testing	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811235	SCV002048608	benign	not provided	2023-01-03	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000077864	SCV000207625	benign	not specified	2015-01-15	no assertion criteria provided	clinical testing