NM_000492.3(CFTR):c.3854C>T (p.Ala1285Val) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Apr 5, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000585919.4

Allele description [Variation Report for NM_000492.3(CFTR):c.3854C>T (p.Ala1285Val)]

NM_000492.3(CFTR):c.3854C>T (p.Ala1285Val)

Gene:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.3(CFTR):c.3854C>T (p.Ala1285Val)
HGVS:
  • NC_000007.14:g.117642574C>T
  • NG_016465.4:g.181791C>T
  • NM_000492.3:c.3854C>T
  • NP_000483.3:p.Ala1285Val
  • LRG_663t1:c.3854C>T
  • LRG_663:g.181791C>T
  • LRG_663p1:p.Ala1285Val
  • NC_000007.13:g.117282628C>T
  • p.Ala1285Val
Protein change:
A1285V
Links:
dbSNP: rs397508617
NCBI 1000 Genomes Browser:
rs397508617
Molecular consequence:
  • NM_000492.3:c.3854C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000696994Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Apr 5, 2021)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of cystic fibrosis variants by polymerase chain reaction/oligonucleotide ligation assay.

Schwartz KM, Pike-Buchanan LL, Muralidharan K, Redman JB, Wilson JA, Jarvis M, Cura MG, Pratt VM.

J Mol Diagn. 2009 May;11(3):211-5. doi: 10.2353/jmoldx.2009.080106. Epub 2009 Mar 26.

PubMed [citation]
PMID:
19324992
PMCID:
PMC2671338

Spectrum and distribution of CFTR gene mutations in asthma and chronic pancreatitis cases of North Indian population.

Muthuswamy S, Agarwal S, Awasthi S, Singh S, Dixit P, Maurya N, Choudhuri G.

Gene. 2014 Apr 10;539(1):125-31. doi: 10.1016/j.gene.2014.01.022. Epub 2014 Jan 14.

PubMed [citation]
PMID:
24440239
See all PubMed Citations (9)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696994.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

Variant summary: CFTR c.3854C>T (p.Ala1285Val) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00066 in 250862 control chromosomes, predominantly at a frequency of 0.0053 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. This frequency is somewhat lower than the maximum expected for a pathogenic variant in CFTR causing Congenital Bilateral Absence of the Vas Deferens (CBAVD) (0.013), allowing no conclusion about variant significance. c.3854C>T has been reported in the literature in an Asian Indian individual affected with CBAVD (Sachdeva 2011). The variant was also found during carrier screening in homozygosity in an Asian Indian (Schwartz 2009) and an Australian individual (Archibald 2017), however the phenotype was not specified in these cases. These reports do not provide unequivocal conclusions about association of the variant with CBAVD. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Another clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Jun 14, 2021

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