NM_000492.4:c.-8G>C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000492.4(CFTR):c.-8G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,613,616 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000492.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.-8G>C | 5_prime_UTR_variant | Exon 1 of 27 | ENST00000003084.11 | NP_000483.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0429 AC: 6527AN: 152004Hom.: 175 Cov.: 32
GnomAD3 exomes AF: 0.0457 AC: 11486AN: 251068Hom.: 364 AF XY: 0.0455 AC XY: 6176AN XY: 135710
GnomAD4 exome AF: 0.0528 AC: 77166AN: 1461494Hom.: 2282 Cov.: 31 AF XY: 0.0519 AC XY: 37759AN XY: 727074
GnomAD4 genome AF: 0.0429 AC: 6529AN: 152122Hom.: 175 Cov.: 32 AF XY: 0.0443 AC XY: 3293AN XY: 74348
ClinVar
Submissions by phenotype
not specified Benign:6
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-8G>C in exon 1 of CFTR: This variant is not expected to have clinical significa nce because it has been identified in 5.5% (477/8600) of European American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington. -
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Cystic fibrosis Benign:4
the variant does not result in CFTR-RD neither -
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This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: BS1, BS2, BS3 -
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. -
not provided Benign:3
This variant is associated with the following publications: (PMID: 30296588, 19652440, 27022295, 15905293) -
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CFTR-related disorder Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
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Hereditary pancreatitis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at