Submissions for variant NM_000321.3(RB1):c.380+12T>C

gnomAD frequency: 0.01087  dbSNP: rs3092881

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078641	SCV000110497	benign	not specified	2013-09-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078641	SCV000303586	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000402398	SCV000384536	benign	Retinoblastoma	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.
GeneDx	RCV000078641	SCV000518993	likely benign	not specified	2016-12-27	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588906	SCV000696569	benign	not provided	2016-05-24	criteria provided, single submitter	clinical testing	Variant summary: The RB1 c.380+12T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 383/118794 control chromosomes (5 homozygotes) at a frequency of 0.0032241, which is approximately 77 times the estimated maximal expected allele frequency of a pathogenic RB1 variant (0.0000417), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000402398	SCV002407115	benign	Retinoblastoma	2024-02-01	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000402398	SCV004017260	benign	Retinoblastoma	2023-07-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588906	SCV004562844	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine	RCV000402398	SCV005046376	likely benign	Retinoblastoma	2024-05-20	criteria provided, single submitter	clinical testing	Case and Pedigree Information: BILATERAL CASES:0, UNILATERAL CASES:1, TOTAL CASES:1, PEDIGREES:1. ACMG Codes Applied:BS1, BP4