7-117479930-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000446805.2(CFTR):c.-191+236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 734,976 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 Uncertain significance (★★).
Frequency
Consequence
ENST00000446805.2 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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CFTR | ENST00000546407.1 | n.166+4122G>A | intron_variant | Intron 2 of 2 | 1 | |||||
CFTR | ENST00000673785.1 | c.-406+14099G>A | intron_variant | Intron 3 of 12 | ENSP00000501235.1 | |||||
CFTR | ENST00000446805.2 | c.-191+236G>A | intron_variant | Intron 3 of 5 | 4 | ENSP00000417012.1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 151750Hom.: 0 Cov.: 29
GnomAD4 exome AF: 0.000111 AC: 65AN: 583226Hom.: 0 Cov.: 6 AF XY: 0.0000853 AC XY: 27AN XY: 316578
GnomAD4 genome AF: 0.000105 AC: 16AN: 151750Hom.: 0 Cov.: 29 AF XY: 0.000108 AC XY: 8AN XY: 74106
ClinVar
Submissions by phenotype
not provided Uncertain:3
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Published functional studies demonstrate a damaging effect as c.-165G>A increases binding of FOXI1 inducing reduced CFTR promoter activity (Lopez et al., 2011); Reported in individuals with congenital absence of the vas deferens (de Meeus et al., 1998; Lopez et al., 2011); Also known as -33G>A; This variant is associated with the following publications: (PMID: 33000223, 10200050, 21948798, 12843327, 20972246) -
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Cystic fibrosis Uncertain:2
This variant occurs in a non-coding region of the CFTR gene. It does not change the encoded amino acid sequence of the CFTR protein. This variant is present in population databases (rs145483167, gnomAD 0.1%). This variant has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 12843327). This variant is also known as -33G>A. ClinVar contains an entry for this variant (Variation ID: 439059). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects CFTR function (PMID: 20972246). 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. -
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CFTR-related disorder Uncertain:1
The CFTR c.-165G>A variant is located in the 5' untranslated region. This variant has been reported in a patient with congenital bilateral absence of the vas deferens and resulted in reduced CFTR transcription in vitro (described as -33G>A in Lopez et al. 2011. PubMed ID: 20972246). This variant is reported in 0.12% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at