ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3067_3072del (p.Ile1023_Val1024del)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.3067_3072del (p.Ile1023_Val1024del)
Variation ID: 38480 Accession: VCV000038480.38
- Type and length
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Deletion, 6 bp
- Location
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Cytogenetic: 7q31.2 7: 117610593-117610598 (GRCh38) [ NCBI UCSC ] 7: 117250647-117250652 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Oct 8, 2024 Sep 24, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3067_3072del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Ile1023_Val1024del inframe deletion NM_000492.3:c.3063_3068delAGTGAT NM_000492.3:c.3067_3072delATAGTG NC_000007.14:g.117610597_117610602del NC_000007.13:g.117250651_117250656del NG_016465.4:g.149814_149819del NG_056128.2:g.3651_3656del LRG_663:g.149814_149819del LRG_663t1:c.3067_3072del LRG_663p1:p.Ile1023_Val1024del - Protein change
- Other names
- CFTR, 3199del6
- Canonical SPDI
- NC_000007.14:117610592:AGTGATAGTG:AGTG
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CFTR | - | - |
GRCh38 GRCh37 |
3816 | 5183 | |
LOC111674472 | - | - | - | GRCh38 | - | 399 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (9) |
reviewed by expert panel
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Sep 24, 2021 | RCV000046775.34 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 13, 2023 | RCV000757083.23 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV001004289.9 | |
CFTR-related disorder
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Pathogenic (2) |
no assertion criteria provided
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Jul 19, 2024 | RCV001826528.10 |
Pathogenic (1) |
criteria provided, single submitter
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Mar 11, 2024 | RCV003473238.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 24, 2021)
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reviewed by expert panel
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR2
Accession: SCV001981576.1
First in ClinVar: Oct 25, 2021 Last updated: Oct 25, 2021 |
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Pathogenic
(Jan 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696944.1
First in ClinVar: Jan 06, 2018 Last updated: Jan 06, 2018 |
Comment:
Variant summary: The c.3067_3072delATAGTG (a.k.a. 3199del6) in CFTR gene is an in-frame deletion that expected to remove Ile1023 and Val1024 from the CFTR protein. Mutation … (more)
Variant summary: The c.3067_3072delATAGTG (a.k.a. 3199del6) in CFTR gene is an in-frame deletion that expected to remove Ile1023 and Val1024 from the CFTR protein. Mutation Taster predicts deleterious outcome. The variant is absent from the large and broad cohorts of the ExAC project. The variant of interest has been identified in multiple affected individuals presented with CF and was referred as causative mutation in peer-reviewed publications. At least one reputable clinical laboratory/diagnostic center classified the variant as Pathogenic. Taking together, the variant was classified as Pathogenic. (less)
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Pathogenic
(Mar 04, 2020)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001425301.1
First in ClinVar: Aug 03, 2020 Last updated: Aug 03, 2020 |
Comment:
c.3067_3072del has been observed in multiple patients presenting with cystic fibrosis in whom a second disease-associated variant was identified. This variant (rs397508492) is rare (<0.1%) … (more)
c.3067_3072del has been observed in multiple patients presenting with cystic fibrosis in whom a second disease-associated variant was identified. This variant (rs397508492) is rare (<0.1%) in a large population dataset (gnomAD: 7/251080 total alleles; 0.002788%; no homozygotes). Additionally, seven submitters in ClinVar classify this variant as either pathogenic or likely pathogenic. We consider this variant to be pathogenic. (less)
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Pathogenic
(Sep 05, 2022)
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criteria provided, single submitter
Method: curation
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002574073.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Comment:
This variant was identified in 4 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a … (more)
This variant was identified in 4 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PM2_SUP, PM3_VSTR, PM4, PP4 (less)
Number of individuals with the variant: 4
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Pathogenic
(Aug 06, 2012)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000331277.4
First in ClinVar: Dec 06, 2016 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Congenital bilateral aplasia of vas deferens from CFTR mutation
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163165.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
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Pathogenic
(Mar 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bronchiectasis with or without elevated sweat chloride 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004213270.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(May 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885187.1
First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019 |
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Likely pathogenic
(Nov 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Mendelics
Accession: SCV000886159.2
First in ClinVar: Jan 06, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Dec 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000074788.9
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This variant, c.3067_3072del, results in the deletion of 2 amino acid(s) of the CFTR protein (p.Ile1023_Val1024del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.3067_3072del, results in the deletion of 2 amino acid(s) of the CFTR protein (p.Ile1023_Val1024del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs397508492, gnomAD 0.01%). This variant has been observed in individual(s) with cystic fibrosis or congenital absence of the vas deferens (PMID: 7516234, 12394343, 15287992, 22020151, 22627569). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 3199del6 or 3195del6. ClinVar contains an entry for this variant (Variation ID: 38480). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002753642.3
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.3067_3072delATAGTG pathogenic mutation (also known as 3199del6, 3195del6, and p.I1023_V1024del) is located in coding exon 19 of the CFTR gene. This pathogenic mutation results … (more)
The c.3067_3072delATAGTG pathogenic mutation (also known as 3199del6, 3195del6, and p.I1023_V1024del) is located in coding exon 19 of the CFTR gene. This pathogenic mutation results from an in-frame deletion of 6 nucleotides at positions 3067 to 3072. This results in the deletion of an isoleucine and a valine residue between codons 1023 and 1024. This mutation was first reported in an individual with cystic fibrosis (CF) in trans with a frameshift alteration (Claustres M et al. Hum. Mol. Genet., 1994 Feb;3:371). In another study, this mutation was identified in trans with a nonsense alteration in an individual with CF with meconium ileus, pulmonary symptoms, pancreatic sufficiency, and elevated sweat chloride levels (Buyse IM et al. Genet. Med.;6:426-30). In a cohort of unrelated French Canadian individuals with CF, 21 of 22 individuals bearing this mutation and another severe CFTR alteration were pancreatic insufficient (Ruchon AF et al. Genet. Med., 2005 Mar;7:210-1). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jan 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003820761.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 29, 2018)
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criteria provided, single submitter
Method: curation
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cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR-France
Accession: SCV001169285.1
First in ClinVar: Mar 14, 2020 Last updated: Mar 14, 2020 |
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Pathogenic
(Dec 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193959.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_000492.3(CFTR):c.3067_3072del6(aka 3199del6) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 15371908, 10798368, 12172395, 15371907, 11668613, … (more)
NM_000492.3(CFTR):c.3067_3072del6(aka 3199del6) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 15371908, 10798368, 12172395, 15371907, 11668613, 8707304, 15371903, 15017334, 15638824, 7516234, 22020151, 18456578, 12394343 and 21679131. Classification of NM_000492.3(CFTR):c.3067_3072del6(aka 3199del6) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Jun 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005196953.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Jul 19, 2024)
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no assertion criteria provided
Method: clinical testing
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CFTR-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005360563.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The CFTR c.3067_3072del6 variant is predicted to result in an in-frame deletion (p.Ile1023_Val1024del). This variant, also referred to as 3199del6 using legacy nomenclature, has been … (more)
The CFTR c.3067_3072del6 variant is predicted to result in an in-frame deletion (p.Ile1023_Val1024del). This variant, also referred to as 3199del6 using legacy nomenclature, has been reported to be causative for cystic fibrosis (see, for example, Buyse et al. 2004. PubMed ID: 15371908; Monaghan et al. 2004. PubMed ID: 15371907; Castellani et al. 2008. PubMed ID: 18456578; Sosnay PR et al 2013. PubMed ID: 23974870; https://cftr2.org). This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD and is interpreted as pathogenic by multiple laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/38480/). Based on the available evidence, we classify this variant as pathogenic. (less)
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002083586.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles. | Terlizzi V | Journal of medical genetics | 2017 | PMID: 27738188 |
The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing. | Schrijver I | The Journal of molecular diagnostics : JMD | 2016 | PMID: 26708955 |
Risk of Misdiagnosis Due to Allele Dropout and False-Positive PCR Artifacts in Molecular Diagnostics: Analysis of 30,769 Genotypes. | Blais J | The Journal of molecular diagnostics : JMD | 2015 | PMID: 26146130 |
Report on the p.Ser489X (p.Ser489*) CFTR mutation, a variant with severe associated phenotype and high prevalence in a Quebec French-Canadian cystic fibrosis patient population. | De Bie I | Genetics in medicine : official journal of the American College of Medical Genetics | 2012 | PMID: 22627569 |
Extensive molecular analysis of patients bearing CFTR-related disorders. | Amato F | The Journal of molecular diagnostics : JMD | 2012 | PMID: 22020151 |
Enhanced frequency of CFTR gene variants in couples who are candidates for assisted reproductive technology treatment. | Tomaiuolo R | Clinical chemistry and laboratory medicine | 2011 | PMID: 21679131 |
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. | Castellani C | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 18456578 |
Frequency and phenotypic consequences of the 3199del6 CFTR mutation in French Canadians. | Ruchon AF | Genetics in medicine : official journal of the American College of Medical Genetics | 2005 | PMID: 15775760 |
Comprehensive cystic fibrosis mutation epidemiology and haplotype characterization in a southern Italian population. | Castaldo G | Annals of human genetics | 2005 | PMID: 15638824 |
High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France. | des Georges M | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2004 | PMID: 15698946 |
Use of MALDI-TOF mass spectrometry in a 51-mutation test for cystic fibrosis: evidence that 3199del6 is a disease-causing mutation. | Buyse IM | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371908 |
Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study. | Monaghan KG | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371907 |
CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. | Sugarman EA | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371903 |
Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. | Watson MS | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371902 |
Are p.I148T, p.R74W and p.D1270N cystic fibrosis causing mutations? | Claustres M | BMC medical genetics | 2004 | PMID: 15287992 |
Frequency of the cystic fibrosis 3199del6 mutation in individuals heterozygous for I148T. | Buller A | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15017334 |
The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis. | Rohlfs EM | Genetics in medicine : official journal of the American College of Medical Genetics | 2002 | PMID: 12394343 |
Cystic fibrosis screening using the College panel: platform comparison and lessons learned from the first 20,000 samples. | Strom CM | Genetics in medicine : official journal of the American College of Medical Genetics | 2002 | PMID: 12172395 |
Improved detection of CFTR mutations in Southern California Hispanic CF patients. | Wong LJ | Human mutation | 2001 | PMID: 11668613 |
Spectrum of CFTR mutations in Mexican cystic fibrosis patients: identification of five novel mutations (W1098C, 846delT, P750L, 4160insGGGG and 297-1G-->A). | Orozco L | Human genetics | 2000 | PMID: 10798368 |
Transcript analysis of CFTR frameshift mutations in lymphocytes using the reverse transcription-polymerase chain reaction technique and the protein truncation test. | Romey MC | Human genetics | 1996 | PMID: 8707304 |
Identification of a 6 bp deletion (3195del6) in exon 17a of the cystic fibrosis (CFTR) gene. | Claustres M | Human molecular genetics | 1994 | PMID: 7516234 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR | - | - | - | - |
https://cftr2.org | - | - | - | - |
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Text-mined citations for rs121908767 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.