rs786205658
Variant summary
Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PM1PM2PM4PP3PP5_Moderate
The NM_000492.4(CFTR):c.1375_1383delTCCACTGGA(p.Ser459_Gly461del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S459S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
CFTR
NM_000492.4 conservative_inframe_deletion
NM_000492.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.10
Publications
1 publications found
Genes affected
CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PM1
In a hotspot region, there are 15 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 16 uncertain in NM_000492.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000492.4.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 7-117548800-GCTGGATCCA-G is Pathogenic according to our data. Variant chr7-117548800-GCTGGATCCA-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 191339.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CFTR | ENST00000003084.11 | c.1375_1383delTCCACTGGA | p.Ser459_Gly461del | conservative_inframe_deletion | Exon 10 of 27 | 1 | NM_000492.4 | ENSP00000003084.6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cystic fibrosis Pathogenic:1
Mar 29, 2024
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Pathogenic:1
-
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance:Likely pathogenic
Review Status:flagged submission
Collection Method:research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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