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NM_000492.4(CFTR):c.273+1G>A AND not specified

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 12, 2017
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:
RCV000780139.1

Allele description [Variation Report for NM_000492.4(CFTR):c.273+1G>A]

NM_000492.4(CFTR):c.273+1G>A

Gene:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.4(CFTR):c.273+1G>A
Other names:
405+1G->A
HGVS:
  • NC_000007.14:g.117509143G>A
  • NG_016465.4:g.48360G>A
  • NG_062452.1:g.781G>A
  • NM_000492.4:c.273+1G>AMANE SELECT
  • LRG_663t1:c.273+1G>A
  • LRG_663:g.48360G>A
  • NC_000007.13:g.117149197G>A
  • NM_000492.3:c.273+1G>A
Links:
dbSNP: rs121908791
NCBI 1000 Genomes Browser:
rs121908791
Molecular consequence:
  • NM_000492.4:c.273+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000917184Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Oct 12, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

A donor splice mutation (405 + 1 G-->A) in cystic fibrosis associated with exon skipping in epithelial CFTR mRNA.

Dörk T, Will K, Demmer A, Tümmler B.

Hum Mol Genet. 1993 Nov;2(11):1965-6. No abstract available.

PubMed [citation]
PMID:
7506605

Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.

Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, Ramalho AS, Amaral MD, Dorfman R, Zielenski J, Masica DL, Karchin R, Millen L, Thomas PJ, Patrinos GP, Corey M, Lewis MH, Rommens JM, Castellani C, Penland CM, Cutting GR.

Nat Genet. 2013 Oct;45(10):1160-7. doi: 10.1038/ng.2745. Epub 2013 Aug 25.

PubMed [citation]
PMID:
23974870
PMCID:
PMC3874936

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917184.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: Variant summary: The CFTR c.273+1G>A variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict significant impact on normal splicing. These predictions were confirmed by a functional study, where authors showed that this change eliminated canonical donor site and lead to exon skipping in epithelial CFTR mRNA, subsequently introducing a frameshift with premature stop codon (Drk_1993). This variant was found in 1/245276 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant of interest has been reported in multiple affected individuals presented with classical CF (Sosnay_2013). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Sep 29, 2024