ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.1140C>T (p.Asp380=)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004329.3(BMPR1A):c.1140C>T (p.Asp380=)
Variation ID: 132691 Accession: VCV000132691.41
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 10q23.2 10: 86919443 (GRCh38) [ NCBI UCSC ] 10: 88679200 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Mar 24, 2015 May 1, 2024 Feb 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_004329.3:c.1140C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Asp380= synonymous NC_000010.11:g.86919443C>T NC_000010.10:g.88679200C>T NG_009362.1:g.167805C>T LRG_298:g.167805C>T LRG_298t1:c.1140C>T LRG_298p1:p.Asp380= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000010.11:86919442:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.01258 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.01258
1000 Genomes Project 30x 0.01280
The Genome Aggregation Database (gnomAD), exomes 0.01460
The Genome Aggregation Database (gnomAD) 0.01512
Exome Aggregation Consortium (ExAC) 0.01535
Trans-Omics for Precision Medicine (TOPMed) 0.01675
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01845
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 | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
BMPR1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2280 | 2374 |
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
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 9, 2016 | RCV000131546.7 | |
Benign (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV001080583.8 | |
Benign (9) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000507545.29 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV001507163.9 | |
Benign (1) |
criteria provided, single submitter
|
Mar 3, 2015 | RCV001705875.2 |
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. |
|
---|---|---|---|---|---|
Benign
(Apr 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602644.3
First in ClinVar: Sep 30, 2017 Last updated: Feb 10, 2020 |
|
|
Benign
(Mar 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000537376.1
First in ClinVar: Mar 24, 2015 Last updated: Mar 24, 2015 |
|
|
Benign
(Aug 12, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806594.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
|
|
Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000365651.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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 … (more)
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001894507.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Benign
(Aug 14, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888816.3
First in ClinVar: Mar 13, 2019 Last updated: Dec 31, 2022 |
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile polyposis syndrome
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016726.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
Benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002549929.4
First in ClinVar: Jul 27, 2022 Last updated: Aug 18, 2023 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000153827.10
First in ClinVar: Jun 03, 2014 Last updated: Feb 28, 2024 |
|
|
Benign
(Nov 21, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186545.9
First in ClinVar: Aug 06, 2014 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)
|
|
Likely benign
(Feb 20, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000787886.1
First in ClinVar: Mar 24, 2015 Last updated: Mar 24, 2015 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553243.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The BMPR1A p.Asp380= variant was identified in 1 of 96 proband chromosomes (frequency: 0.01) from one individual with Hereditary hemorrhagic telangiectasia; however, the variant is … (more)
The BMPR1A p.Asp380= variant was identified in 1 of 96 proband chromosomes (frequency: 0.01) from one individual with Hereditary hemorrhagic telangiectasia; however, the variant is identified as a polymorphism (Lesca 2006). The variant was also identified in the following databases: dbSNP (ID: rs35572415) as "With Likely benign allele", ClinVar (5x benign, 1x likely benign), Clinvitae, and LOVD 3.0 (4x). The variant was not identified in Cosmic or the MutDB database. The variant was identified in control databases in 3968 of 276746 chromosomes (34 homozygous) at a frequency of 0.01 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 92 of 24020 chromosomes (freq: 0.004), Other in 129 of 6460 chromosomes (freq: 0.02), Latino in 477 of 34416 chromosomes (freq: 0.01), European in 2719 of 126260 chromosomes (freq: 0.02), Ashkenazi Jewish in 149 of 10150 chromosomes (freq: 0.01), Finnish in 154 of 25792 chromosomes (freq: 0.006), and South Asian in 248 of 30782 chromosomes (freq: 0.008). The variant was not observed in the East Asian population. A study by Pyatt 2006 investigating Juvenile polyposis syndrome listed this variant as a polymorphism. The p.Asp380= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less)
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807726.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001920507.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955117.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037020.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
click to load more click to collapse |
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
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
[Chronic anaemia in a patient with hereditary haemorrhagic telangiectasia and juvenile gastric polyposis]. | Blaas SH | Deutsche medizinische Wochenschrift (1946) | 2006 | PMID: 16902903 |
Distribution of ENG and ACVRL1 (ALK1) mutations in French HHT patients. | Lesca G | Human mutation | 2006 | PMID: 16705692 |
Mutation screening in juvenile polyposis syndrome. | Pyatt RE | The Journal of molecular diagnostics : JMD | 2006 | PMID: 16436638 |
Text-mined citations for rs35572415 ...
HelpRecord last updated May 01, 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.