chr7-117603694-T-G
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000492.4(CFTR):c.2820T>G(p.Thr940=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,614,126 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T940T) has been classified as Likely benign.
Frequency
Consequence
NM_000492.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.2820T>G | p.Thr940= | synonymous_variant | 17/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.2820T>G | p.Thr940= | synonymous_variant | 17/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00135 AC: 205AN: 152228Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000334 AC: 84AN: 251408Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135864
GnomAD4 exome AF: 0.000129 AC: 188AN: 1461780Hom.: 0 Cov.: 32 AF XY: 0.000117 AC XY: 85AN XY: 727188
GnomAD4 genome ? AF: 0.00135 AC: 205AN: 152346Hom.: 2 Cov.: 32 AF XY: 0.00136 AC XY: 101AN XY: 74494
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:1Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Jul 23, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 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 | Core Molecular Diagnostic Lab, McGill University Health Centre | May 21, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 06, 2019 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital | Dec 29, 2015 | - - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 15, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 28, 2019 | Variant summary: CFTR c.2820T>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00044 in 277144 control chromosomes, predominantly at a frequency of 0.0045 within the African subpopulation in the gnomAD database. This frequency is somewhat lower than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (0.0045 vs 0.013), nevertheless the variant still might represent a benign polymorphism. To our knowledge, no occurrence of c.2820T>G in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1 benign, 1 likely benign, 1 VUS). Based on the evidence outlined above, the variant was classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Thr940Thr in exon 17 of CFTR: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.5% (21/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs60887846). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 23, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jan 30, 2023 | - - |
Hereditary pancreatitis Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 04, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at