rs4148700
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000492.4(CFTR):c.744-9_744-6del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,535,716 control chromosomes in the GnomAD database, including 38,096 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.23 ( 4348 hom., cov: 25)
Exomes 𝑓: 0.21 ( 33748 hom. )
Consequence
CFTR
NM_000492.4 intron
NM_000492.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.82
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 -16 ACMG points.
BP6
?
Variant 7-117536514-AGATT-A is Benign according to our data. Variant chr7-117536514-AGATT-A is described in ClinVar as [Benign]. Clinvar id is 43579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117536514-AGATT-A is described in Lovd as [Benign]. Variant chr7-117536514-AGATT-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.744-9_744-6del | intron_variant | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.744-9_744-6del | intron_variant | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.232 AC: 35190AN: 151540Hom.: 4333 Cov.: 25
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GnomAD3 exomes AF: 0.270 AC: 44068AN: 163440Hom.: 6756 AF XY: 0.267 AC XY: 23220AN XY: 86906
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GnomAD4 exome AF: 0.212 AC: 292985AN: 1384058Hom.: 33748 AF XY: 0.215 AC XY: 147376AN XY: 684806
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GnomAD4 genome ? AF: 0.232 AC: 35245AN: 151658Hom.: 4348 Cov.: 25 AF XY: 0.242 AC XY: 17941AN XY: 74088
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 20, 2011 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cystic fibrosis Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2014 | 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. - |
Benign, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | the variant does not result in CFTR-RD neither - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 20, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 30, 2023 | - - |
CFTR-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 15, 2017 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at