ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.49A>C (p.Ile17Leu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(8); Benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004329.3(BMPR1A):c.49A>C (p.Ile17Leu)
Variation ID: 231113 Accession: VCV000231113.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86876067 (GRCh38) [ NCBI UCSC ] 10: 88635824 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 19, 2017 Oct 8, 2024 Jul 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004329.3:c.49A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Ile17Leu missense NC_000010.11:g.86876067A>C NC_000010.10:g.88635824A>C NG_009362.1:g.124429A>C LRG_298:g.124429A>C LRG_298t1:c.49A>C LRG_298p1:p.Ile17Leu - Protein change
- I17L
- Other names
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- Canonical SPDI
- NC_000010.11:86876066:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BMPR1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2325 | 2421 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Apr 13, 2023 | RCV000216319.13 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Nov 4, 2019 | RCV000758774.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 15, 2024 | RCV001193976.2 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV000701225.10 | |
BMPR1A-related disorder
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Uncertain significance (1) |
no assertion criteria provided
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Feb 15, 2024 | RCV003982966.2 |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 29, 2023 | RCV003475014.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Nov 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001791446.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
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Uncertain significance
(Jul 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000887604.2
First in ClinVar: Mar 14, 2019 Last updated: Jan 01, 2022 |
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Uncertain significance
(Sep 25, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002528606.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
To the best of our knowledge, the BMPR1A c.49A>C (p.I17L) variant has not been reported in the literature. It was observed in 7/34592 chromosomes of … (more)
To the best of our knowledge, the BMPR1A c.49A>C (p.I17L) variant has not been reported in the literature. It was observed in 7/34592 chromosomes of the Latino subpopulation, with no homozygotes, in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID 231113). Functional studies have not been performed, and in silico predictions of the variant's effect on protein function are inconclusive. The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(Apr 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000912932.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces isoleucine with leucine at codon 17 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces isoleucine with leucine at codon 17 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 7/251326 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. (less)
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Uncertain significance
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000830016.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 17 of the BMPR1A protein (p.Ile17Leu). … (more)
This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 17 of the BMPR1A protein (p.Ile17Leu). This variant is present in population databases (rs778886055, gnomAD 0.02%). 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: 231113). 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%. 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. (less)
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Benign
(Sep 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000274861.7
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
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 … (more)
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. (less)
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Uncertain significance
(Jul 15, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001363176.2
First in ClinVar: Jun 22, 2020 Last updated: Sep 16, 2024 |
Comment:
Variant summary: BMPR1A c.49A>C (p.Ile17Leu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: BMPR1A c.49A>C (p.Ile17Leu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251326 control chromosomes, predominantly in the Latino cohort with an allele frequency of 0.0002. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.49A>C in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 231113). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Sep 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Polyposis syndrome, hereditary mixed, 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004210973.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain Significance
(Dec 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Juvenile polyposis syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004840681.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces isoleucine with leucine at codon 17 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces isoleucine with leucine at codon 17 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 7/251326 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. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Feb 15, 2024)
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no assertion criteria provided
Method: clinical testing
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BMPR1A-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004796762.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The BMPR1A c.49A>C variant is predicted to result in the amino acid substitution p.Ile17Leu. To our knowledge, this variant has not been reported in the … (more)
The BMPR1A c.49A>C variant is predicted to result in the amino acid substitution p.Ile17Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD, indicating it is rare. This variant is interpreted by vast majority of the submitters in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/231113/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs778886055 ...
HelpRecord last updated Oct 13, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.