NM_000492.4(CFTR):c.4243-7del AND Cystic fibrosis

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 11, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000227990.11

Allele description [Variation Report for NM_000492.4(CFTR):c.4243-7del]

NM_000492.4(CFTR):c.4243-7del

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC111674477:CFTR intron 23 enhancer [Gene]

Variant type:

Deletion

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.4243-7del

HGVS:

NC_000007.14:g.117666901del
NG_016465.4:g.206118del
NG_056133.2:g.1307del
NM_000492.4:c.4243-7delMANE SELECT
LRG_663t1:c.4243-7del
LRG_663:g.206118del
NC_000007.13:g.117306953del
NC_000007.13:g.117306955del
NM_000492.3:c.4243-7del
NM_000492.3:c.4243-7delT

Links:

dbSNP: rs878854021

NCBI 1000 Genomes Browser:

rs878854021

Molecular consequence:

NM_000492.4:c.4243-7del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Cystic fibrosis (CF)
Synonyms:: Mucoviscidosis
Identifiers:: MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

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Clinical outcome of stage UICC II colon cancer patients
Accession: GDS4513

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BioProject Links for BioSample (Select 4429462) (2)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000285007	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 11, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004024521	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 6, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000285007

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 11, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004024521

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 6, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV000285007.8

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

#	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

From Johns Hopkins Genomics, Johns Hopkins University, SCV004024521.2

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

Description

This CFTR intronic variant (rs878854021) is rare (<0.1%) in a large population dataset (gnomADv3.1.2: 6/152142 total alleles; 0.004%; no homozygotes) and has been reported in ClinVar (Variation ID:237857). It has not been reported in the literature in individuals with cystic fibrosis, to our knowledge. Bioinformatic analysis predicts that this intronic variant may weaken the native acceptor splice site although this has not been confirmed experimentally to our knowledge. We consider the clinical significance of CFTR c.4243-7del to be uncertain at this time.

#	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: May 19, 2024

ClinVar

Relating variation to medicine