ClinVar Miner

Submissions for variant NM_000760.4(CSF3R):c.1253G>A (p.Arg418His)

gnomAD frequency: 0.00006  dbSNP: rs564880597
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002022237 SCV002262266 uncertain significance Autosomal recessive severe congenital neutropenia due to CSF3R deficiency 2023-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 418 of the CSF3R protein (p.Arg418His). This variant is present in population databases (rs564880597, gnomAD 0.008%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CSF3R protein function. ClinVar contains an entry for this variant (Variation ID: 1481195). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002022237 SCV005402431 uncertain significance Autosomal recessive severe congenital neutropenia due to CSF3R deficiency 2024-05-07 criteria provided, single submitter clinical testing The CSF3R c.1253G>A (p.Arg418His) missense change has a maximum subpopulation frequency of 0.0080% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with CSF3R-related severe congenital neutropenia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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