Submissions for variant NM_001297.5(CNGB1):c.3115G>A (p.Gly1039Arg)

gnomAD frequency: 0.00372  dbSNP: rs148999583

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000177529	SCV000229412	likely benign	not specified	2014-10-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000989610	SCV000398307	uncertain significance	Retinitis pigmentosa	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000761936	SCV000568998	uncertain significance	not provided	2017-04-17	criteria provided, single submitter	clinical testing	The c.3115 G>A variant in the CNGB1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3115 G>A variant is observed in 301/66256 (0.45%) alleles from individuals of European background, including one homozygous individual, in the ExAC dataset (Lek et al., 2016). In-silico splice models predict that c.3115 G>A may create a cryptic splice acceptor site that could supplant the natural splice acceptor site. However, in the absence of RNA/functional studies, the actual effect of the c.3115 G>A change in this individual is unknown. If c.3115 G>A does not alter splicing, it will result in the G1039R missense change. The G1039R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret c.3115 G>A as a variant of uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000761936	SCV000892163	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000989610	SCV001140116	likely benign	Retinitis pigmentosa	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV000761936	SCV001646495	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002517713	SCV003684196	uncertain significance	Inborn genetic diseases	2021-09-16	criteria provided, single submitter	clinical testing	The c.3115G>A (p.G1039R) alteration is located in exon 31 (coding exon 30) of the CNGB1 gene. This alteration results from a G to A substitution at nucleotide position 3115, causing the glycine (G) at amino acid position 1039 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003937605	SCV004753769	likely benign	CNGB1-related disorder	2019-09-12	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000761936	SCV001920349	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000761936	SCV001968023	likely benign	not provided		no assertion criteria provided	clinical testing