17-80099763-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_017950.4(CCDC40):c.3417A>G(p.Pro1139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,612,434 control chromosomes in the GnomAD database, including 171,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_017950.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.492 AC: 74666AN: 151786Hom.: 18954 Cov.: 31
GnomAD3 exomes AF: 0.451 AC: 111378AN: 247100Hom.: 26325 AF XY: 0.461 AC XY: 61985AN XY: 134524
GnomAD4 exome AF: 0.454 AC: 662967AN: 1460530Hom.: 152785 Cov.: 50 AF XY: 0.457 AC XY: 331983AN XY: 726564
GnomAD4 genome AF: 0.492 AC: 74734AN: 151904Hom.: 18977 Cov.: 31 AF XY: 0.491 AC XY: 36484AN XY: 74242
ClinVar
Submissions by phenotype
not specified Benign:4
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Pro1139Pro in exon 20 of CCDC40: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 44.7% (3724/8334) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2304854). -
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Primary ciliary dyskinesia Benign:3
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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. -
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Primary ciliary dyskinesia 15 Benign:3
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:2
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Glycogen storage disease, type II Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at