ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.1412G>A (p.Arg471His)

gnomAD frequency: 0.00001  dbSNP: rs779371501
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000580005 SCV000682866 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-20 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 471 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies performed are not sufficient to determine the impact of this variant on BMPR1A protein function (PMID: 29522511). This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 3/251488 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000703304 SCV000832200 uncertain significance Juvenile polyposis syndrome 2024-01-20 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 471 of the BMPR1A protein (p.Arg471His). This variant is present in population databases (rs779371501, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 489687). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt BMPR1A function with a negative predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BMPR1A function (PMID: 29522511). 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.
Ambry Genetics RCV000580005 SCV001171797 benign Hereditary cancer-predisposing syndrome 2023-04-07 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284275 SCV001469972 uncertain significance not provided 2019-11-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000703304 SCV004836017 uncertain significance Juvenile polyposis syndrome 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 471 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/251488 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV004568259 SCV005058191 uncertain significance Polyposis syndrome, hereditary mixed, 2 2023-12-14 criteria provided, single submitter clinical testing

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