chr7-117540157-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000492.4(CFTR):c.927C>T(p.Ala309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,388 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
CFTR
NM_000492.4 synonymous
NM_000492.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.572
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 7-117540157-C-T is Benign according to our data. Variant chr7-117540157-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 256258.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.927C>T | p.Ala309= | synonymous_variant | 8/27 | ENST00000003084.11 | NP_000483.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.927C>T | p.Ala309= | synonymous_variant | 8/27 | 1 | NM_000492.4 | ENSP00000003084 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251120Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135744
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461388Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727004
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GnomAD4 genome Cov.: 32
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32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cystic fibrosis Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2022 | The c.927C>T variant (also known as p.A309A), located in coding exon 8 of the CFTR gene, results from a C to T substitution at nucleotide position 927. This nucleotide substitution does not change the alanine at codon 309. This alteration has been identified in an individual diagnosed with pancreatitis (Lee JH et al. Hum Mol Genet, 2003 Sep;12:2321-32). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at