rs121909001
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PM4_Supporting
The NM_000492.4(CFTR):c.1522_1524del(p.Phe508del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F508F) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
CFTR
NM_000492.4 inframe_deletion
NM_000492.4 inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.54
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a hotspot region, there are 8 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 10 uncertain in NM_000492.4
PM4
?
Nonframeshift variant in NON repetitive region in NM_000492.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.1522_1524del | p.Phe508del | inframe_deletion | 11/27 | ENST00000003084.11 | |
CFTR-AS1 | NR_149084.1 | n.221+1138_221+1140del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.1522_1524del | p.Phe508del | inframe_deletion | 11/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at