ClinVar Miner

Submissions for variant NM_000823.4(GHRHR):c.1146+4T>A

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002624623 SCV003517504 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the GHRHR gene. It does not directly change the encoded amino acid sequence of the GHRHR protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368440035, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GHRHR-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004783019 SCV005395154 uncertain significance not specified 2024-09-09 criteria provided, single submitter clinical testing Variant summary: GHRHR c.1146+4T>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.6e-05 in 251494 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in GHRHR causing Isolated growth hormone deficiency, type 4, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1146+4T>A in individuals affected with Isolated growth hormone deficiency, type 4 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2197019). Based on the evidence outlined above, the variant was classified as 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.