ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.690C>A (p.Phe230Leu)

gnomAD frequency: 0.00008  dbSNP: rs185747820
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001167411 SCV001329907 uncertain significance Primary hyperoxaluria, type II 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, 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.
Invitae RCV001355504 SCV001699049 likely benign not provided 2024-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002365817 SCV002661919 uncertain significance Nephrolithiasis/nephrocalcinosis 2021-07-27 criteria provided, single submitter clinical testing The p.F230L variant (also known as c.690C>A), located in coding exon 7 of the GRHPR gene, results from a C to A substitution at nucleotide position 690. The phenylalanine at codon 230 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355504 SCV001550413 uncertain significance not provided no assertion criteria provided clinical testing The GRHPR p.Phe230Leu variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs185747820) and in control databases in 35 of 282812 chromosomes at a frequency of 0.0001238 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Latino in 13 of 35428 chromosomes (freq: 0.000367), Other in 2 of 7224 chromosomes (freq: 0.000277) and European (non-Finnish) in 20 of 129138 chromosomes (freq: 0.000155), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.Phe230 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. 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. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.