The RIMS1 c.5071C>T (p.Arg1691Ter) variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is located in the last exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, the p.Arg1691Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for cone-rod dystrophy, dominant.
ClinVar Genomic variation as it relates to human health
NM_014989.7(RIMS1):c.5071C>T (p.Arg1691Ter)
Germline
Classification
Help
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.
(2)
Help
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
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_014989.7(RIMS1):c.5071C>T (p.Arg1691Ter)
Variation ID: 631988 Accession: VCV000631988.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q13 6: 72400706 (GRCh38) [ NCBI UCSC ] 6: 73110408 (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 May 27, 2019 Feb 20, 2024 Aug 28, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_014989.7:c.5071C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055804.2:p.Arg1691Ter nonsense NM_001168407.2:c.3031C>T NP_001161879.1:p.Arg1011Ter nonsense NM_001168408.2:c.2446C>T NP_001161880.1:p.Arg816Ter nonsense NM_001168409.2:c.2275C>T NP_001161881.1:p.Arg759Ter nonsense NM_001168410.2:c.2473C>T NP_001161882.1:p.Arg825Ter nonsense NM_001168411.2:c.652C>T NP_001161883.1:p.Arg218Ter nonsense NM_001350414.2:c.2992C>T NP_001337343.1:p.Arg998Ter nonsense NM_001350415.2:c.3088C>T NP_001337344.1:p.Arg1030Ter nonsense NM_001350416.2:c.3037C>T NP_001337345.1:p.Arg1013Ter nonsense NM_001350417.2:c.2518C>T NP_001337346.1:p.Arg840Ter nonsense NM_001350418.2:c.3010C>T NP_001337347.1:p.Arg1004Ter nonsense NM_001350419.2:c.2290C>T NP_001337348.1:p.Arg764Ter nonsense NM_001350420.2:c.3145C>T NP_001337349.1:p.Arg1049Ter nonsense NM_001350421.2:c.2890C>T NP_001337350.1:p.Arg964Ter nonsense NM_001350422.2:c.2515C>T NP_001337351.1:p.Arg839Ter nonsense NM_001350423.2:c.2779C>T NP_001337352.1:p.Arg927Ter nonsense NM_001350424.2:c.2377C>T NP_001337353.1:p.Arg793Ter nonsense NM_001350425.2:c.2989C>T NP_001337354.1:p.Arg997Ter nonsense NM_001350426.2:c.2365C>T NP_001337355.1:p.Arg789Ter nonsense NM_001350427.2:c.2443C>T NP_001337356.1:p.Arg815Ter nonsense NM_001350428.2:c.2449C>T NP_001337357.1:p.Arg817Ter nonsense NM_001350429.2:c.2809C>T NP_001337358.1:p.Arg937Ter nonsense NM_001350430.2:c.2446C>T NP_001337359.1:p.Arg816Ter nonsense NM_001350431.2:c.3127C>T NP_001337360.1:p.Arg1043Ter nonsense NM_001350432.2:c.2353C>T NP_001337361.1:p.Arg785Ter nonsense NM_001350433.2:c.3118C>T NP_001337362.1:p.Arg1040Ter nonsense NM_001350434.2:c.2593C>T NP_001337363.1:p.Arg865Ter nonsense NM_001350435.2:c.2980C>T NP_001337364.1:p.Arg994Ter nonsense NM_001350436.2:c.3223C>T NP_001337365.1:p.Arg1075Ter nonsense NM_001350437.2:c.2974C>T NP_001337366.1:p.Arg992Ter nonsense NM_001350438.2:c.2698C>T NP_001337367.1:p.Arg900Ter nonsense NM_001350439.2:c.2962C>T NP_001337368.1:p.Arg988Ter nonsense NM_001350440.2:c.2362C>T NP_001337369.1:p.Arg788Ter nonsense NM_001350441.2:c.2959C>T NP_001337370.1:p.Arg987Ter nonsense NM_001350442.2:c.2701C>T NP_001337371.1:p.Arg901Ter nonsense NM_001350443.2:c.2932C>T NP_001337372.1:p.Arg978Ter nonsense NM_001350444.2:c.2806C>T NP_001337373.1:p.Arg936Ter nonsense NM_001350445.2:c.2599C>T NP_001337374.1:p.Arg867Ter nonsense NM_001350446.2:c.3217C>T NP_001337375.1:p.Arg1073Ter nonsense NM_001350447.2:c.2878C>T NP_001337376.1:p.Arg960Ter nonsense NM_001350448.2:c.3034C>T NP_001337377.1:p.Arg1012Ter nonsense NM_001350449.2:c.2425C>T NP_001337378.1:p.Arg809Ter nonsense NM_001350450.2:c.2374C>T NP_001337379.1:p.Arg792Ter nonsense NM_001350454.2:c.2941C>T NP_001337383.1:p.Arg981Ter nonsense NM_001350455.2:c.2293C>T NP_001337384.1:p.Arg765Ter nonsense NM_001350456.2:c.3214C>T NP_001337385.1:p.Arg1072Ter nonsense NM_001350457.2:c.2971C>T NP_001337386.1:p.Arg991Ter nonsense NM_001350458.2:c.3040C>T NP_001337387.1:p.Arg1014Ter nonsense NM_001350459.2:c.2893C>T NP_001337388.1:p.Arg965Ter nonsense NM_001350460.2:c.2911C>T NP_001337389.1:p.Arg971Ter nonsense NM_001350461.2:c.2761C>T NP_001337390.1:p.Arg921Ter nonsense NM_001350462.2:c.3076C>T NP_001337391.1:p.Arg1026Ter nonsense NM_001350463.2:c.2716C>T NP_001337392.1:p.Arg906Ter nonsense NM_001350464.2:c.2719C>T NP_001337393.1:p.Arg907Ter nonsense NM_001350465.2:c.2203C>T NP_001337394.1:p.Arg735Ter nonsense NM_001350466.2:c.2722C>T NP_001337395.1:p.Arg908Ter nonsense NM_001350467.2:c.2638C>T NP_001337396.1:p.Arg880Ter nonsense NM_001350468.2:c.2563C>T NP_001337397.1:p.Arg855Ter nonsense NM_001350469.2:c.2791C>T NP_001337398.1:p.Arg931Ter nonsense NM_001350470.2:c.2479C>T NP_001337399.1:p.Arg827Ter nonsense NM_001350471.2:c.2872C>T NP_001337400.1:p.Arg958Ter nonsense NM_001350472.2:c.2398C>T NP_001337401.1:p.Arg800Ter nonsense NM_001350473.2:c.2401C>T NP_001337402.1:p.Arg801Ter nonsense NM_001350474.2:c.2764C>T NP_001337403.1:p.Arg922Ter nonsense NC_000006.12:g.72400706C>T NC_000006.11:g.73110408C>T NG_016209.1:g.518759C>T - Protein change
- R1691*, R1026*, R1073*, R218*, R789*, R801*, R816*, R817*, R855*, R900*, R907*, R965*, R981*, R987*, R1011*, R1014*, R759*, R765*, R788*, R792*, R793*, R800*, R809*, R815*, R840*, R865*, R901*, R921*, R936*, R960*, R991*, R992*, R994*, R1004*, R1012*, R1013*, R1040*, R1072*, R735*, R764*, R827*, R880*, R937*, R971*, R998*, R1030*, R1043*, R1049*, R1075*, R785*, R825*, R839*, R867*, R906*, R908*, R922*, R927*, R931*, R958*, R964*, R978*, R988*, R997*
- Other names
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- Canonical SPDI
- NC_000006.12:72400705:C:T
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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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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
- Links
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. |
|||
| RIMS1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1141 | 1188 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000778802.4 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 28, 2023 | RCV003727822.2 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cone-rod dystrophy 7
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000915182.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The RIMS1 c.5071C>T (p.Arg1691Ter) variant is a stop-gained variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. … (more)
The RIMS1 c.5071C>T (p.Arg1691Ter) variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is located in the last exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, the p.Arg1691Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for cone-rod dystrophy, dominant. (less)
|
|
|
Uncertain significance
(Aug 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004540498.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. ClinVar contains an entry for this variant (Variation ID: 631988). This premature translational stop signal has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 33090715). This variant is present in population databases (rs528476500, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg1691*) in the RIMS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the RIMS1 protein. (less)
|
Comment:
Comment:
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. ClinVar contains an entry for this variant (Variation ID: 631988). This premature translational stop signal has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 33090715). This variant is present in population databases (rs528476500, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg1691*) in the RIMS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the RIMS1 protein.
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:
The RIMS1 c.5071C>T (p.Arg1691Ter) variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is located in the last exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, the p.Arg1691Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for cone-rod dystrophy, dominant.
Comment:
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. ClinVar contains an entry for this variant (Variation ID: 631988). This premature translational stop signal has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 33090715). This variant is present in population databases (rs528476500, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg1691*) in the RIMS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the RIMS1 protein.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non-syndromic inherited retinal dystrophies. | Liu X | Clinical & experimental ophthalmology | 2021 | PMID: 33090715 |
Text-mined citations for rs528476500 ...
HelpThese 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 Sep 29, 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.