NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter) AND not specified

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 5, 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:: RCV000780159.9

Allele description [Variation Report for NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)]

NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)

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.3846G>A (p.Trp1282Ter)

HGVS:

NC_000007.14:g.117642566G>A
NG_016465.4:g.181783G>A
NM_000492.4:c.3846G>AMANE SELECT
NP_000483.3:p.Trp1282Ter
NP_000483.3:p.Trp1282Ter
LRG_663t1:c.3846G>A
LRG_663:g.181783G>A
LRG_663p1:p.Trp1282Ter
NC_000007.13:g.117282620G>A
NM_000492.3:c.3846G>A
NM_000492.4:c.3846G>A
p.Trp1282*
p.Trp1282X

Protein change:

W1282*; TRP1282TER

Links:

Genetic Testing Registry (GTR): GTR000074114; Genetic Testing Registry (GTR): GTR000500233; OMIM: 602421.0022; dbSNP: rs77010898

NCBI 1000 Genomes Browser:

rs77010898

Molecular consequence:

NM_000492.4:c.3846G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000917207	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 5, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12767731, 27707539, 23974870 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000917207

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 5, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study.

McKone EF, Emerson SS, Edwards KL, Aitken ML.

Lancet. 2003 May 17;361(9370):1671-6.

PubMed [citation]

PMID:: 12767731

Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation.

Mutyam V, Libby EF, Peng N, Hadjiliadis D, Bonk M, Solomon GM, Rowe SM.

J Cyst Fibros. 2017 Jan;16(1):24-29. doi: 10.1016/j.jcf.2016.09.005. Epub 2016 Oct 1.

PubMed [citation]

PMID:: 27707539
PMCID:: PMC5241185

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917207.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: The CFTR c.3846G>A (p.Trp1282X) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 46/120654 control chromosomes at a frequency of 0.0003813, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant is a common disease variant reported in numerous affected individuals in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic, including CFTR2. Taken together, this variant is classified 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: Oct 13, 2024

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