chr7-117548629-T-TGTG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000492.4(CFTR):c.1210-12_1210-11insGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000885 in 1,491,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000492.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.1210-12_1210-11insGTG | intron_variant | Intron 9 of 26 | ENST00000003084.11 | NP_000483.3 | ||
CFTR-AS1 | NR_149084.1 | n.222-6091_222-6090insCAC | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000901 AC: 12AN: 133130Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000884 AC: 120AN: 1357984Hom.: 0 Cov.: 37 AF XY: 0.000101 AC XY: 68AN XY: 676374
GnomAD4 genome AF: 0.0000901 AC: 12AN: 133216Hom.: 0 Cov.: 32 AF XY: 0.0000773 AC XY: 5AN XY: 64656
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:1
This variant consists of 13 TG and 6 T nucleotide repeats and is located in intron 9 of the CFTR gene. While this variant is present in population databases (rs397843667), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a CFTR-related disease. However, it occurs on the opposite chromosome (in trans) from a pathogenic variant in CFTR in an unaffected individual (Invitae database). Considering that biallelic pathogenic variants in CFTR are expected to cause cystic fibrosis or congenital bilateral absence of the vas deferens (CBAVD), this evidence indicates this TG[13]T[6] allele is not a primary cause of disease. Different TG variants, TG[11]T6 and TG[12]T[6], have been reported in individuals affected with bronchial asthma and chronic bronchitis, as well as healthy individuals (PMID: 18350634, 23554779). A different TG13 variant, TG[13]T[5] is known to induce skipping of exon 9, and has been observed in individuals affected with CBAVD and cystic fibrosis (PMID: 10556281, 14685937), while the TG[13]T[7] variant has only been reported in controls (PMID: 24551851). 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. -
not provided Uncertain:1
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CFTR-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at