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NM_000492.4(CFTR):c.3764C>A (p.Ser1255Ter) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jun 28, 2022
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:
RCV001810834.14

Allele description [Variation Report for NM_000492.4(CFTR):c.3764C>A (p.Ser1255Ter)]

NM_000492.4(CFTR):c.3764C>A (p.Ser1255Ter)

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.3764C>A (p.Ser1255Ter)
Other names:
p.Ser1255*
HGVS:
  • NC_000007.14:g.117642484C>A
  • NG_016465.4:g.181701C>A
  • NM_000492.4:c.3764C>AMANE SELECT
  • NP_000483.3:p.Ser1255Ter
  • NP_000483.3:p.Ser1255Ter
  • LRG_663t1:c.3764C>A
  • LRG_663:g.181701C>A
  • LRG_663p1:p.Ser1255Ter
  • NC_000007.13:g.117282538C>A
  • NM_000492.3:c.3764C>A
  • p.Ser1255X
Protein change:
S1255*; SER1255TER
Links:
Genetic Testing Registry (GTR): GTR000074114; OMIM: 602421.0021; dbSNP: rs76649725
NCBI 1000 Genomes Browser:
rs76649725
Molecular consequence:
  • NM_000492.4:c.3764C>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
2

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001474556ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Pathogenic
(Sep 25, 2019) 		germlineclinical testing

Citation Link,

SCV004226578Mayo Clinic Laboratories, Mayo Clinic
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 28, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot providednot providednot providedclinical 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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001474556.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CFTR c.3764C>A; p.Ser1255Ter variant (rs76649725) is reported in the literature in multiple individuals affected with cystic fibrosis (Behar 2017, Cutting 1990, Macek 1997, CFTR2 database). In at least one affected individual, this variant was confirmed in trans to a second pathogenic variant (Cutting 1990). Several other reports indicate this variant also occurs in cis to a missense variant, p.Ile1203Val (Behar 2017, Cutting 1992). The p.Ser1255Ter variant is found on only two chromosomes (2/251034 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: CFTR2 database: https://cftr2.org Behar DM et al. Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening. Mol Genet Genomic Med. 2017 Feb 19;5(3):223-236. Cutting GR et al. Analysis of four diverse population groups indicates that a subset of cystic fibrosis mutations occur in common among Caucasians. Am J Hum Genet. 1992 Jun;50(6):1185-94. Cutting GR et al. Two patients with cystic fibrosis, nonsense mutations in each cystic fibrosis gene, and mild pulmonary disease. N Engl J Med. 1990 Dec 13;323(24):1685-9. Macek M Jr et al. Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%. Am J Hum Genet. 1997 May;60(5):1122-7.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226578.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

PM2, PM3_strong, PVS1

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

Last Updated: Oct 13, 2024