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NM_000088.4(COL1A1):c.1462-3C>A AND Osteogenesis imperfecta type I

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 10, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001899990.4

Allele description [Variation Report for NM_000088.4(COL1A1):c.1462-3C>A]

NM_000088.4(COL1A1):c.1462-3C>A

Gene:
COL1A1:collagen type I alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.33
Genomic location:
Preferred name:
NM_000088.4(COL1A1):c.1462-3C>A
HGVS:
  • NC_000017.11:g.50194629G>T
  • NG_007400.1:g.12011C>A
  • NM_000088.3:c.1462-3C>A
  • NM_000088.4:c.1462-3C>AMANE SELECT
  • LRG_1t1:c.1462-3C>A
  • LRG_1:g.12011C>A
  • NC_000017.10:g.48271990G>T
Links:
dbSNP: rs2144572314
NCBI 1000 Genomes Browser:
rs2144572314
Molecular consequence:
  • NM_000088.4:c.1462-3C>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Osteogenesis imperfecta type I (OI1)
Synonyms:
OI, TYPE I; Osteogenesis imperfecta type 1; OI type 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008146; MedGen: C0023931; Orphanet: 666; OMIM: 166200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002123906Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 10, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular Outcome, Prediction, and Clinical Consequences of Splice Variants in COL1A1, Which Encodes the proα1(I) Chains of Type I Procollagen.

Schleit J, Bailey SS, Tran T, Chen D, Stowers S, Schwarze U, Byers PH.

Hum Mutat. 2015 Jul;36(7):728-39. doi: 10.1002/humu.22812.

PubMed [citation]
PMID:
25963598

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002123906.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change falls in intron 21 of the COL1A1 gene. It does not directly change the encoded amino acid sequence of the COL1A1 protein. It affects a nucleotide within the consensus splice site. 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. This variant disrupts the c.1462-3C nucleotide in the COL1A1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 25963598). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 1362073). This variant has not been reported in the literature in individuals affected with COL1A1-related conditions. This variant is not present in population databases (gnomAD no frequency).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024