ClinVar Genomic variation as it relates to human health
NM_001134363.3(RBM20):c.3265C>G (p.Pro1089Ala)
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(2); Benign(5); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001134363.3(RBM20):c.3265C>G (p.Pro1089Ala)
Variation ID: 44006 Accession: VCV000044006.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q25.2 10: 110821884 (GRCh38) [ NCBI UCSC ] 10: 112581642 (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 Mar 8, 2017 May 1, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001134363.3:c.3265C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001127835.2:p.Pro1089Ala missense NC_000010.11:g.110821884C>G NC_000010.10:g.112581642C>G NG_021177.1:g.182488C>G LRG_382:g.182488C>G LRG_382t1:c.3265C>G LRG_382p1:p.Pro1089Ala NP_001127835.1:p.Pro1089Ala - Protein change
- P1089A
- Other names
- p.P1089A:CCC>GCC
- Canonical SPDI
- NC_000010.11:110821883:C:G
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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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0.00260 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00234
The Genome Aggregation Database (gnomAD) 0.00252
1000 Genomes Project 0.00260
Trans-Omics for Precision Medicine (TOPMed) 0.00267
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
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. |
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RBM20 | - | - |
GRCh38 GRCh37 |
1848 | 1883 |
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. |
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Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Apr 26, 2021 | RCV000036981.17 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000467697.16 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 25, 2019 | RCV000252850.5 | |
Benign (1) |
criteria provided, single submitter
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Nov 9, 2017 | RCV001170931.2 | |
Likely benign (1) |
no assertion criteria provided
|
- | RCV001727524.1 |
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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Benign
(Oct 14, 2016)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000236367.6
First in ClinVar: Jul 05, 2015 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Aug 12, 2015)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000111390.8
First in ClinVar: Jan 17, 2014 Last updated: Mar 08, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(May 01, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060637.6
First in ClinVar: May 03, 2013 Last updated: Mar 08, 2017 |
Comment:
Variant classified as Uncertain Significance - Favor Benign. The Pro1089Ala vari ant (RBM20) has not been reported in the literature nor previously identified by our … (more)
Variant classified as Uncertain Significance - Favor Benign. The Pro1089Ala vari ant (RBM20) has not been reported in the literature nor previously identified by our laboratory. Proline (Pro) at position 1089 is not well conserved in evolut ion, suggesting that a change may be tolerated. Other computational analyses (bi ochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) a lso suggest that this variant may not impact the protein, though this informatio n is not predictive enough to rule out pathogenicity. Of note, the variant has b een identified in the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS). However, the data did not pass quality metrics and was therefore not i ncluded in the assessment of the variant. In summary, although this data support s that the Pro1089Ala variant may be benign, additional studies are needed to fu lly assess its clinical significance. (less)
Number of individuals with the variant: 1
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Likely benign
(Dec 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433492.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
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Benign
(Apr 26, 2021)
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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: SCV001623205.1
First in ClinVar: May 23, 2021 Last updated: May 23, 2021 |
Comment:
Variant summary: RBM20 c.3265C>G (p.Pro1089Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Variant summary: RBM20 c.3265C>G (p.Pro1089Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00045 in 156498 control chromosomes, predominantly at a frequency of 0.0077 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 164 fold of the estimated maximal expected allele frequency for a pathogenic variant in RBM20 causing Dilated Cardiomyopathy phenotype (4.7e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign/likely benign n=6, VUS n=1). Based on the evidence outlined above, the variant was classified as benign. (less)
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Uncertain significance
(May 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1DD
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000611430.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
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Benign
(Nov 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333581.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1DD
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000562792.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
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Likely benign
(Sep 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1DD
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004564923.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
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Likely benign
(Jan 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000319867.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely 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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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001918922.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932369.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971873.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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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
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RBM20 | - | - | - | - |
Text-mined citations for rs147356378 ...
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.