NM_000492.3(CFTR):c.3718-2477C>T AND CFTR-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 31, 2023
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:: RCV001826438.11

Allele description [Variation Report for NM_000492.3(CFTR):c.3718-2477C>T]

NM_000492.3(CFTR):c.3718-2477C>T

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC113633877:CFTR intron 19 DNase I hypersensitive site [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.3(CFTR):c.3718-2477C>T

Other names:

3849+10kbC->T; 3849+10kbC>T

HGVS:

NC_000007.14:g.117639961C>T
NG_016465.4:g.179178C>T
NG_062449.1:g.167C>T
NM_000492.4:c.3718-2477C>TMANE SELECT
LRG_663t1:c.3718-2477C>T
LRG_663:g.179178C>T
NC_000007.13:g.117280015C>T
c.3717+12191C>T
NM_000492.3:c.3718-2477C>T

Nucleotide change:

3849+10KB, C-T

Links:

Cystic Fibrosis Mutation Database: 518; Genetic Testing Registry (GTR): GTR000500233; OMIM: 602421.0062; dbSNP: rs75039782

NCBI 1000 Genomes Browser:

rs75039782

Molecular consequence:

NM_000492.4:c.3718-2477C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: CFTR-related disorder (CFTR-RD)
Synonyms:: CFTR-related disorders; CFTR-related condition
Identifiers:: MedGen: C5924204

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002075873	Natera, Inc.	no assertion criteria provided	Pathogenic (Jul 26, 2017)	germline	clinical testing
SCV004114477	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 31, 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

SCV002075873

Natera, Inc.

no assertion criteria provided

Pathogenic
(Jul 26, 2017)

germline

clinical testing

SCV004114477

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 31, 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

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 Natera, Inc., SCV002075873.1

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

#	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 PreventionGenetics, part of Exact Sciences, SCV004114477.1

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

Description

The CFTR c.3718-2477C>T variant is predicted to interfere with splicing. This variant is also referred to as 3849+10kbC>T or c.3717+12191C>T. This variant has previously been reported to be causative in multiple cystic fibrosis patients with a mild phenotype (Highsmith et al. 1994. PubMed ID: 7521937; McKone et al. 2003. PubMed ID: 12767731; Duguépéroux et al. 2005. PubMed ID: 15738290; Sosnay et al. 2013. PubMed ID: 23974870; cftr2.org) and is included in the American College Medical Genetics (ACMG) panel of CF variants (Watson et al. 2004. PubMed ID: 15371902; Deignan JL et al. 2023. PubMed ID: 37310422). We classify this variant as pathogenic.

#	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: Dec 7, 2024

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