NM_000094.4(COL7A1):c.5701-1G>T AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 29, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000498204.3

Allele description [Variation Report for NM_000094.4(COL7A1):c.5701-1G>T]

NM_000094.4(COL7A1):c.5701-1G>T

Gene:

COL7A1:collagen type VII alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000094.4(COL7A1):c.5701-1G>T

HGVS:

NC_000003.12:g.48576558C>A
NG_007065.1:g.23695G>T
NM_000094.4:c.5701-1G>TMANE SELECT
LRG_286t1:c.5701-1G>T
LRG_286:g.23695G>T
NC_000003.11:g.48613991C>A
NM_000094.3:c.5701-1G>T

Links:

dbSNP: rs1553855868

NCBI 1000 Genomes Browser:

rs1553855868

Molecular consequence:

NM_000094.4:c.5701-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Pseudomonas aeruginosa strain HARRAN_VET_OK28 NODE_7_length_431927_cov_117.72589...
Pseudomonas aeruginosa strain HARRAN_VET_OK28 NODE_7_length_431927_cov_117.725896, whole genome shotgun sequence
gi|2183290414|ref|NZ_JAKGDP01000000 gnl|WGS:NZ_JAKGDP01|NODE_7_length_431927_cov_117.725896

Nucleotide
Pseudomonas aeruginosa strain ADU_VET_ST3 NODE_61_length_253_cov_0.829545, whole...
Pseudomonas aeruginosa strain ADU_VET_ST3 NODE_61_length_253_cov_0.829545, whole genome shotgun sequence
gi|2183287213|ref|NZ_JAKGDU01000006 gnl|WGS:NZ_JAKGDU01|NODE_61_length_253_cov_0.829545

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000589630	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Feb 8, 2016)	germline	clinical testing	Citation Link,
SCV004292730	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 29, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25566895, 27899325, 16199547, 16971478, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000589630

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Feb 8, 2016)

germline

clinical testing

Citation Link,

SCV004292730

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 29, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Epidermolysis bullosa pruriginosa: a case with a novel mutation and co-existent lichen amyloidosus.

Chen Q, Lee JS, Tey HL.

Indian J Dermatol Venereol Leprol. 2015 Jan-Feb;81(1):40-2. doi: 10.4103/0378-6323.148565.

PubMed [citation]

PMID:: 25566895

Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages.

Vahidnezhad H, Youssefian L, Zeinali S, Saeidian AH, Sotoudeh S, Mozafari N, Abiri M, Kajbafzadeh AM, Barzegar M, Ertel A, Fortina P, Uitto J.

J Invest Dermatol. 2017 Mar;137(3):660-669. doi: 10.1016/j.jid.2016.10.023. Epub 2016 Oct 27.

PubMed [citation]

PMID:: 27899325

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000589630.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.5701-1 G>T pathogenic variant in the COL7A1 gene has been reported previously in association with RDEB(Chen et al., 2015). This splice site variant destroys the canonical splice acceptor site in intron 67. It is predicted tocause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNAdecay, or to an abnormal protein product if the message is used for protein translation. The c.5701-1 G>T variant wasnot observed in approximately 6500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. We interpret c.5701-1 G>T asa pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292730.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Disruption of this splice site has been observed in individual(s) with autosomal dominant epidermolysis bullosa and/or autosomal recessive epidermolysis bullosa dystrophica (PMID: 25566895, 27899325). For these reasons, this variant has been classified as Pathogenic. 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: 431992). This variant is also known as IVS67-1G>T. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 67 of the COL7A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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