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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 8, 2020
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:: RCV000224473.4

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:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000281210	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 19, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001470299	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Sep 8, 2020)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15948195, 11336401, 7506605, 22975760, 23974870, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000281210

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 19, 2015)

germline

clinical testing

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

SCV001470299

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Sep 8, 2020)

unknown

clinical testing

PubMed (6)
[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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to carrier screening.

Quint A, Lerer I, Sagi M, Abeliovich D.

Am J Med Genet A. 2005 Jul 30;136(3):246-8.

PubMed [citation]

PMID:: 15948195

See all PubMed Citations (7)

Details of each submission

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000281210.2

#	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	not provided	not provided	not provided	not provided		not provided	0.000068	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470299.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The variant is located in a canonical splice-donor site and interferes with normal CFTR mRNA splicing. The variant has been reported in individuals affected with cystic fibrosis in the published literature (PMID: 22975760 (2013), 23974870 (2013), 15948195 (2005), 11336401 (2001), 7506605 (1993)). The variant has been shown to result in a frameshift resulting in premature termination of protein synthesis (PMID: 7506605 (1993)). The frequency of this variant in the general population is consistent with pathogenicity. Therefore, the variant is classified as pathogenic.

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

Last Updated: Sep 29, 2024

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