ClinVar Genomic variation as it relates to human health
NM_001848.3(COL6A1):c.717+4A>G
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.
Pathogenic(1); Likely pathogenic(1); Uncertain significance(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001848.3(COL6A1):c.717+4A>G
Variation ID: 284826 Accession: VCV000284826.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.3 21: 45987076 (GRCh38) [ NCBI UCSC ] 21: 47406990 (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 Dec 6, 2016 Feb 20, 2024 Sep 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001848.3:c.717+4A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000021.9:g.45987076A>G NC_000021.8:g.47406990A>G NG_008674.1:g.10328A>G LRG_475:g.10328A>G LRG_475t1:c.717+4A>G - Protein change
- Other names
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- Canonical SPDI
- NC_000021.9:45987075:A: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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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00005
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00012
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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COL6A1 | - | - |
GRCh38 GRCh37 |
1771 | 1880 |
Conditions - Germline
Condition
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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
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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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Sep 8, 2023 | RCV000653543.8 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Aug 5, 2021 | RCV000725541.11 |
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
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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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Pathogenic
(Jun 23, 2016)
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criteria provided, single submitter
Method: clinical testing
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Bethlem myopathy 1A
Affected status: yes
Allele origin:
unknown
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Study: Clinvar_gadteam_Clinical_exome_analysis_3
Accession: SCV000803836.1 First in ClinVar: May 28, 2018 Last updated: May 28, 2018 |
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Likely pathogenic
(Mar 09, 2018)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000337615.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 7
Sex: mixed
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Uncertain significance
(Apr 10, 2020)
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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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GeneDx
Accession: SCV000582906.4
First in ClinVar: Dec 06, 2016 Last updated: Sep 24, 2021 |
Comment:
In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 32065942, 30564623, 32403337)
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Uncertain significance
(Aug 05, 2021)
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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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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501836.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Uncertain significance
(Jul 24, 2019)
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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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Revvity Omics, Revvity
Accession: SCV003833819.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Sep 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bethlem myopathy 1A
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000775424.6
First in ClinVar: May 28, 2018 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 284826). This variant has been observed in individuals with clinical features of COL6A1-related conditions (PMID: 30564623, 32065942, 32403337, 32528171; Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 5 of the COL6A1 gene. It does not directly change the encoded amino acid sequence of the COL6A1 protein. It affects a nucleotide within the consensus splice site. (less)
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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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Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness. | Töpf A | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32528171 |
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain. | Gonzalez-Quereda L | Genes | 2020 | PMID: 32403337 |
Clinical features of collagen VI-related dystrophies: A large Brazilian cohort. | Zanoteli E | Clinical neurology and neurosurgery | 2020 | PMID: 32065942 |
Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients. | Nallamilli BRR | Annals of clinical and translational neurology | 2018 | PMID: 30564623 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL6A1 | - | - | - | - |
Text-mined citations for rs762867111 ...
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.