ClinVar Genomic variation as it relates to human health
NM_019098.5(CNGB3):c.607C>T (p.Arg203Ter)
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
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NM_019098.5(CNGB3):c.607C>T (p.Arg203Ter)
Variation ID: 5223 Accession: VCV000005223.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q21.3 8: 86668055 (GRCh38) [ NCBI UCSC ] 8: 87680283 (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 Apr 4, 2013 Apr 15, 2024 Jan 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_019098.5:c.607C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_061971.3:p.Arg203Ter nonsense NC_000008.11:g.86668055G>A NC_000008.10:g.87680283G>A NG_016980.1:g.80621C>T - Protein change
- R203*
- Other names
- CNGB3, 607C-T, ARG203TER
- Canonical SPDI
- NC_000008.11:86668054:G:A
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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 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
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
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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CNGB3 | - | - |
GRCh38 GRCh37 |
1218 | 1262 |
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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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Oct 11, 2019 | RCV000005533.8 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 16, 2020 | RCV001272489.1 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV001068378.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 13, 2019 | RCV001074242.1 |
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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Likely pathogenic
(Nov 14, 2014)
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criteria provided, single submitter
Method: literature only
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Achromatopsia 3
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220887.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Jan 04, 2024)
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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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Invitae
Accession: SCV001233487.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg203*) in the CNGB3 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg203*) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). This variant is present in population databases (rs267606739, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with achromatopsia, early-onset retinal dystrophy, and/or Leber congenital amaurosis (PMID: 10958649, 25205868, 27874104, 29186038). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5223). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001239815.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Oct 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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Achromatopsia 3
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001482634.1 First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The c.607C>T (p.R203*) variant has been previously reported as pathogenic [PMID 10958649, … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The c.607C>T (p.R203*) variant has been previously reported as pathogenic [PMID 10958649, 27874104, 29186038, 25525159] (less)
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Pathogenic
(Sep 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004042348.5
First in ClinVar: Oct 14, 2023 Last updated: Apr 15, 2024 |
Comment:
CNGB3: PM3:Very Strong, PVS1, PM2
Number of individuals with the variant: 1
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Pathogenic
(Mar 27, 2017)
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no assertion criteria provided
Method: research
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ACHM3
Affected status: yes
Allele origin:
germline
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Molecular Genetics Laboratory, Institute for Ophthalmic Research
Accession: SCV000575824.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
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Pathogenic
(Sep 01, 2000)
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no assertion criteria provided
Method: literature only
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ACHROMATOPSIA 3
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000025715.2
First in ClinVar: Apr 04, 2013 Last updated: Jul 07, 2022 |
Comment on evidence:
Kohl et al. (2000) reported 2 male sibs with achromatopsia (262300) who were compound heterozygotes for a 1-bp deletion (605080.0002) and a C-to-T transition at … (more)
Kohl et al. (2000) reported 2 male sibs with achromatopsia (262300) who were compound heterozygotes for a 1-bp deletion (605080.0002) and a C-to-T transition at position 607, resulting in a premature stop codon. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Achromatopsia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001454555.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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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Molecular Screening of 43 Brazilian Families Diagnosed with Leber Congenital Amaurosis or Early-Onset Severe Retinal Dystrophy. | Porto FBO | Genes | 2017 | PMID: 29186038 |
CNGB3 mutation spectrum including copy number variations in 552 achromatopsia patients. | Mayer AK | Human mutation | 2017 | PMID: 28795510 |
Identifying mutations in Tunisian families with retinal dystrophy. | Habibi I | Scientific reports | 2016 | PMID: 27874104 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
CNGB3-achromatopsia clinical trial with CNTF: diminished rod pathway responses with no evidence of improvement in cone function. | Zein WM | Investigative ophthalmology & visual science | 2014 | PMID: 25205868 |
CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. | Kohl S | European journal of human genetics : EJHG | 2005 | PMID: 15657609 |
Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. | Kohl S | Human molecular genetics | 2000 | PMID: 10958649 |
Text-mined citations for rs267606739 ...
HelpRecord last updated Apr 15, 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.