chr7-117479869-G-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000546407.1(CFTR):n.166+4061G>T 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 0.00146 in 593,708 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0039 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00062 ( 1 hom. )
Consequence
CFTR
ENST00000546407.1 intron, non_coding_transcript
ENST00000546407.1 intron, non_coding_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.54
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 7-117479869-G-T is Benign according to our data. Variant chr7-117479869-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 51031.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=4, Benign=1, Likely_benign=2}.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
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+4061G>T | intron_variant, non_coding_transcript_variant | 1 | |||||
CFTR | ENST00000446805.2 | c.-191+175G>T | intron_variant | 4 | |||||
CFTR | ENST00000673785.1 | c.-406+14038G>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00387 AC: 587AN: 151620Hom.: 2 Cov.: 31
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GnomAD4 exome AF: 0.000620 AC: 274AN: 441970Hom.: 1 Cov.: 3 AF XY: 0.000534 AC XY: 125AN XY: 233892
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GnomAD4 genome ? AF: 0.00391 AC: 593AN: 151738Hom.: 2 Cov.: 31 AF XY: 0.00359 AC XY: 266AN XY: 74148
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:4Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 15, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 15, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2023 | Describes a nucleotide substitution 226 basepairs upstream of the ATG translational start site in the 5' untranslated region (UTR); Identified in individuals with cystic fibrosis in published literature, but in whom a second CFTR variant was either not detected or not specified (Romey 1999, des Georges 2008, Zeiger 2020); Published functional studies demonstrate decreased Sp1 and USF DNA-binding and decreased transcriptional activity in one study that utilized a core promoter construct, but the associated transcriptional activity was not significantly different from wild type in a second study that utilized a full-length promoter construct (Taulan 2007, Ott 2012); Also known as c.-94G>T; This variant is associated with the following publications: (PMID: 12939925, 26656651, 11168023, 31665830, 18832460, 21948798, 10204861, 17678620, 37313453) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 04, 2023 | In the published literature, this variant has been reported in individuals with cystic fibrosis (PMIDs: 31665830 (2020), 18832460 (2008), 11168023 (2001), 10204861 (1999)). Functional studies indicate this variant may impact promoter activity but not at a significant difference from the wild type (PMIDs: 17678620 (2007), 21948798 (2012)). The frequency of this variant in the general population, 0.014 (117/8656 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 02, 2021 | - - |
Cystic fibrosis Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at