rs74349463
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_213607.3(CCDC103):c.276+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,454 control chromosomes in the GnomAD database, including 19,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 1376 hom., cov: 32)
Exomes 𝑓: 0.15 ( 18379 hom. )
Consequence
CCDC103
NM_213607.3 splice_donor_region, intron
NM_213607.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.08650
2
Clinical Significance
Conservation
PhyloP100: 0.298
Genes affected
CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 17-44901658-T-C is Benign according to our data. Variant chr17-44901658-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 263318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC103 | NM_213607.3 | c.276+6T>C | splice_donor_region_variant, intron_variant | ENST00000417826.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC103 | ENST00000417826.3 | c.276+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_213607.3 | P1 | |||
CCDC103 | ENST00000357776.6 | c.276+6T>C | splice_donor_region_variant, intron_variant | 2 | |||||
CCDC103 | ENST00000410006.6 | c.276+6T>C | splice_donor_region_variant, intron_variant | 2 | P1 | ||||
CCDC103 | ENST00000410027.5 | c.276+6T>C | splice_donor_region_variant, intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.126 AC: 19130AN: 152086Hom.: 1378 Cov.: 32
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GnomAD3 exomes AF: 0.134 AC: 33561AN: 250970Hom.: 2708 AF XY: 0.140 AC XY: 18960AN XY: 135622
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GnomAD4 exome AF: 0.155 AC: 226189AN: 1461250Hom.: 18379 Cov.: 32 AF XY: 0.156 AC XY: 113169AN XY: 726926
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GnomAD4 genome ? AF: 0.126 AC: 19125AN: 152204Hom.: 1376 Cov.: 32 AF XY: 0.123 AC XY: 9187AN XY: 74398
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Primary ciliary dyskinesia 17 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at