VCV000044004.31 - ClinVar

NM_001134363.3(RBM20):c.3170G>A (p.Arg1057Gln)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

7 out of 12 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001134363.3(RBM20):c.3170G>A (p.Arg1057Gln)

Variation ID: 44004 Accession: VCV000044004.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q25.2 10: 110821789 (GRCh38) [ NCBI UCSC ] 10: 112581547 (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	May 29, 2016	Apr 13, 2025	Feb 4, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001134363.3:c.3170G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001127835.2:p.Arg1057Gln	missense
NC_000010.11:g.110821789G>A
NC_000010.10:g.112581547G>A
NG_021177.1:g.182393G>A
LRG_382:g.182393G>A
LRG_382t1:c.3170G>A

... more HGVS ... less HGVS

Protein change

R1057Q

Other names

p.R1057Q:CGG>CAG

Canonical SPDI

NC_000010.11:110821788:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.01757 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00296

The Genome Aggregation Database (gnomAD), exomes 0.00343

The Genome Aggregation Database (gnomAD), exomes 0.00928

1000 Genomes Project 0.01757

1000 Genomes Project 30x 0.01780

Exome Aggregation Consortium (ExAC) 0.01902

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00066

The Genome Aggregation Database (gnomAD) 0.00107

Trans-Omics for Precision Medicine (TOPMed) 0.00214

Links

ClinGen: CA133356 dbSNP: rs188054898 VarSome

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
Gene	OMIM	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.
RBM20		-	-	GRCh38 GRCh37	2154	2190

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.
not specified	Benign (5)	criteria provided, multiple submitters, no conflicts	Mar 24, 2015	RCV000036979.15
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Sep 4, 2015	RCV000619887.4
Dilated cardiomyopathy 1DD	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 4, 2025	RCV000225935.19
Cardiomyopathy	Benign (1)	criteria provided, single submitter	Feb 26, 2016	RCV000770282.3
not provided	Likely benign (2)	no assertion criteria provided	-	RCV001705666.2

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 (Dec 31, 2014) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060635.6 First in ClinVar: May 03, 2013 Last updated: May 29, 2016	Comment: p.Arg1057Gln in exon 11 of RBM20: This variant is not expected to have clinical significance because it has been identified in 4.8% (381/7990) of South … (more) p.Arg1057Gln in exon 11 of RBM20: This variant is not expected to have clinical significance because it has been identified in 4.8% (381/7990) of South Asian ch romosomes by the by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs188054898). In addition, this variant is not conserved acros s species, including mammals. Of note, >10 mammals a glutamine (Gln) at this pos ition despite high nearby amino acid conservation. (less) Number of individuals with the variant: 14

Benign (Sep 04, 2015) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000735129.5 First in ClinVar: Apr 14, 2018 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)

Benign (Feb 26, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Study: Canadian Open Genetics Repository Accession: SCV000901714.1 First in ClinVar: May 06, 2019 Last updated: May 06, 2019

Benign (Mar 24, 2014) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000171327.10 First in ClinVar: Jun 23, 2014 Last updated: May 29, 2016	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)

Likely benign (Jan 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Dilated cardiomyopathy 1DD Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000360371.3 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)

Benign (Feb 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Dilated cardiomyopathy 1DD Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000286200.9 First in ClinVar: Jul 01, 2016 Last updated: Feb 25, 2025

Benign (Mar 24, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000225275.6 First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RBM20 http://www.ncbi.nlm.nih.gov/vari… http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/?chr=10&from=112581547&to=112581547 Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed

Benign (-) N Not contributing to aggregate classification	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: SCV001953956.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	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: SCV001967405.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	Dilated cardiomyopathy 1DD Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000732927.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018

Benign (-) N Not contributing to aggregate classification	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: SCV001925712.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001928728.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021

click to load more submissions click to collapse

Comment:

p.Arg1057Gln in exon 11 of RBM20: This variant is not expected to have clinical significance because it has been identified in 4.8% (381/7990) of South Asian ch romosomes by the by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs188054898). In addition, this variant is not conserved acros s species, including mammals. Of note, >10 mammals a glutamine (Gln) at this pos ition despite high nearby amino acid conservation.

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 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.

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 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.

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 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RBM20	-	-	-	-

Text-mined citations for rs188054898 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 17, 2025

ClinVar Genomic variation as it relates to human health

NM_001134363.3(RBM20):c.3170G>A (p.Arg1057Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs188054898 ...