rs145483167
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000546407.1(CFTR):n.166+4122G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 734,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
CFTR
ENST00000546407.1 intron, non_coding_transcript
ENST00000546407.1 intron, non_coding_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.167
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 made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000546407.1 | n.166+4122G>A | intron_variant, non_coding_transcript_variant | 1 | |||||
CFTR | ENST00000446805.2 | c.-191+236G>A | intron_variant | 4 | |||||
CFTR | ENST00000673785.1 | c.-406+14099G>A | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 151750Hom.: 0 Cov.: 29
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GnomAD4 exome AF: 0.000111 AC: 65AN: 583226Hom.: 0 Cov.: 6 AF XY: 0.0000853 AC XY: 27AN XY: 316578
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 151750Hom.: 0 Cov.: 29 AF XY: 0.000108 AC XY: 8AN XY: 74106
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cystic fibrosis Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This variant occurs in a non-coding region of the CFTR gene. It does not change the encoded amino acid sequence of the CFTR protein. This variant is present in population databases (rs145483167, gnomAD 0.1%). This variant has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 12843327). This variant is also known as -33G>A. ClinVar contains an entry for this variant (Variation ID: 439059). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects CFTR function (PMID: 20972246). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 28, 2017 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 19, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 28, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at