ClinVar Genomic variation as it relates to human health
NM_000093.5(COL5A1):c.738C>T (p.Thr246=)
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_000093.5(COL5A1):c.738C>T (p.Thr246=)
Variation ID: 136922 Accession: VCV000136922.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.3 9: 134727349 (GRCh38) [ NCBI UCSC ] 9: 137619195 (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 Oct 2, 2016 Feb 14, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000093.5:c.738C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000084.3:p.Thr246= synonymous NM_001278074.1:c.738C>T NP_001265003.1:p.Thr246= synonymous NC_000009.12:g.134727349C>T NC_000009.11:g.137619195C>T NG_008030.1:g.90544C>T LRG_737:g.90544C>T LRG_737t1:c.738C>T LRG_737p1:p.Thr246= LRG_737t2:c.738C>T LRG_737p2:p.Thr246= - Protein change
- Other names
- p.T246T:ACC>ACT
- Canonical SPDI
- NC_000009.12:134727348: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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0.34265 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.34265
Trans-Omics for Precision Medicine (TOPMed) 0.35089
The Genome Aggregation Database (gnomAD) 0.34823
1000 Genomes Project 30x 0.33901
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.33215
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
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. |
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COL5A1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2612 | 3393 |
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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Benign (5) |
criteria provided, multiple submitters, no conflicts
|
Nov 13, 2012 | RCV000124481.19 | |
Benign (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000374462.12 | |
Benign (1) |
criteria provided, single submitter
|
Mar 15, 2017 | RCV000589836.8 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV001513760.15 | |
Benign (1) |
criteria provided, single submitter
|
Jul 30, 2021 | RCV001657783.9 | |
Benign (1) |
criteria provided, single submitter
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Dec 29, 2014 | RCV002312849.8 |
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
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000302248.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Ehlers-Danlos Syndrome, Type VIIA
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000478508.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
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Benign
(Mar 15, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695402.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The COL5A1 c.738C>T (p.Thr246Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. The variant is not found within … (more)
Variant summary: The COL5A1 c.738C>T (p.Thr246Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. The variant is not found within a known functional domain and one in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not significantly affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 52060/121340 control chromosomes (12029 homozygotes) at a frequency of 0.4290424, which is approximately 343234 times the estimated maximal expected allele frequency of a pathogenic COL5A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. Several publications have cited the variant as a common polymorphism (Symoens_HM_2012; Takahara_AJHG_2002). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. (less)
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Benign
(Nov 13, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167914.12
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 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)
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Benign
(Jul 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Ehlers-Danlos syndrome, classic type, 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001876284.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Sex: mixed
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Benign
(Jul 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fibromuscular dysplasia, multifocal
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001876295.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Sex: mixed
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Benign
(Dec 29, 2014)
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criteria provided, single submitter
Method: clinical testing
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Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000738281.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: 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)
Number of individuals with the variant: 1
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ehlers-Danlos syndrome, classic type, 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001721435.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024 |
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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, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001806896.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 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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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740176.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 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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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: SCV001976051.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 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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Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria. | Symoens S | Human mutation | 2012 | PMID: 22696272 |
Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I. | Takahara K | American journal of human genetics | 2002 | PMID: 12145749 |
Text-mined citations for rs3124299 ...
HelpRecord last updated Apr 20, 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.