Submissions for variant NM_004333.6(BRAF):c.-5A>G (rs71645936)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123874	SCV000167218	benign	not specified	2013-04-08	criteria provided, single submitter	clinical testing	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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000123874	SCV000337858	likely benign	not specified	2015-12-04	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000407859	SCV000467004	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 Clinical Services Laboratory,Illumina	RCV000301216	SCV000467005	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.
Illumina Clinical Services Laboratory,Illumina	RCV000335004	SCV000467006	likely benign	Cardio-facio-cutaneous syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000587286	SCV000698343	benign	not provided	2017-02-27	criteria provided, single submitter	clinical testing	Variant summary: The BRAF c.-5A>G variant involves the alteration of a non-conserved nucleotide in 5 UTR region. This variant was found in 10/5008 control chromosomes from 1000 Genomes at a frequency of 0.0019968, which is approximately 799 times the estimated maximal expected allele frequency of a pathogenic BRAF variant (0.0000025. The variant is found in East Asian population with an allele frequency of 1% (10/1008), suggesting it is a benign polymorphism mainly found in East Asian population. The allele frequency of this variant in ExAC and gnomad (early version) is 1.5% (2/130 chromosomes) and 1.3% (97/7260 chromosomes), respectively. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign/likely benign. Taken together, this variant is classified as Benign.