NM_000094.4(COL7A1):c.5532+1G>A AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 9, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000094.4(COL7A1):c.5532+1G>A]


COL7A1:collagen type VII alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
Other names:
  • NC_000003.12:g.48578320C>T
  • NG_007065.1:g.21933G>A
  • NM_000094.3:c.5532+1G>A
  • NM_000094.4:c.5532+1G>AMANE SELECT
  • LRG_286t1:c.5532+1G>A
  • LRG_286:g.21933G>A
  • NC_000003.11:g.48615753C>T
Nucleotide change:
IVS64DS, G-A, +1
OMIM: 120120.0018; dbSNP: rs767182886
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000094.3:c.5532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_000094.4:c.5532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000680735GeneDxcriteria provided, single submitter
(Nov 29, 2017)
germlineclinical testing

Citation Link,

SCV001575674Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 9, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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



Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa.

Mellerio JE, Ashton GH, Mohammedi R, Lyon CC, Kirby B, Harman KE, Salas-Alanis JC, Atherton DJ, Harrison PV, Griffiths WA, Black MM, Eady RA, McGrath JA.

J Invest Dermatol. 1999 Jun;112(6):984-7.

PubMed [citation]

Novel and recurrent COL7A1 mutations in Chilean patients with dystrophic epidermolysis bullosa.

Rodríguez FA, Gana MJ, Yubero MJ, Zillmann G, Krämer SM, Catalán J, Rubio-Astudillo J, González S, Liu L, Ozoemena L, Mellerio JE, McGrath JA, Palisson F, Conget P.

J Dermatol Sci. 2012 Feb;65(2):149-52. doi: 10.1016/j.jdermsci.2011.11.010. Epub 2011 Dec 13. No abstract available. Erratum in: J Dermatol Sci. 2012 Apr;66(1):85. Mellerio, Jemima M [corrected to Mellerio, Jemima E].

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000680735.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


The c.5532+1 G>A splice site variant has been previously reported as an apparently de novo variant in association with autosomal recessive DEB (Mellerio et al., 1999; Shipman et al., 2014). This variant destroys the canonical splice donor site in intron 64, and is expected to cause abnormal gene splicing. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001575674.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)


This sequence change affects a donor splice site in intron 64 of the COL7A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs767182886, ExAC 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of epidermolysis bullosa dystrophica (PMID: 10383749, 22209565). ClinVar contains an entry for this variant (Variation ID: 488825). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jul 7, 2021

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