ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.45_53del (p.Ala16_Ala18del) (rs572454921)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000173106 SCV000224191 benign not specified 2014-08-25 criteria provided, single submitter clinical testing
Invitae RCV000231673 SCV000284628 benign Retinoblastoma 2020-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492473 SCV000580866 benign Hereditary cancer-predisposing syndrome 2017-11-30 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Co-occurence with mutation in same gene (phase unknown);Subpopulation frequency in support of benign classification
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286262 SCV001472801 benign none provided 2020-05-28 criteria provided, single submitter clinical testing
GeneDx RCV001354146 SCV001884291 benign not provided 2016-07-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327)
ITMI RCV000173106 SCV000086119 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354146 SCV001548689 likely benign not provided no assertion criteria provided clinical testing The RB1 p.Ala16_Ala18del variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs572454921) and in ClinVar (classified as Benign by Invitae, Ambry Genetics and EGL Genetic Diagnostics. Conditions associated as Retinoblastoma and Hereditary cancer-predisposing syndrome). The variant was identified in control databases in 110 of 105 080 chromosomes (3 homozygous) at a frequency of 0.001047 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African  in 60 of 1 794 chromosomes (freq: 0.0334), European (Non-Finnish)  in 3 of 38 746 chromosomes (freq: 0.000077), Latino  in 41 of 21 494 chromosomes (freq: 0.00191), South Asian  in 5 of 19 876 chromosomes (freq: 0.000252), and Other  in 1 of 3 226 chromosomes (freq: 0.000309); it was not observed in the Ashkenazi Jewish, East Asian and European (Finnish) populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. This variant is an in-frame deletion resulting in the removal of Ala residues between codons 16-18; the impact of this alteration on RB1 protein function is not known. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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