rs753716586
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017950.4(CCDC40):c.3180+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,613,700 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_017950.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.3180+6C>G | splice_region_variant, intron_variant | ENST00000397545.9 | NP_060420.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.3180+6C>G | splice_region_variant, intron_variant | 5 | NM_017950.4 | ENSP00000380679.4 | ||||
CCDC40 | ENST00000574799.5 | n.2717+6C>G | splice_region_variant, intron_variant | 1 | ||||||
CCDC40 | ENST00000572253.5 | n.3437C>G | non_coding_transcript_exon_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000603 AC: 15AN: 248938Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135228
GnomAD4 exome AF: 0.000107 AC: 156AN: 1461522Hom.: 1 Cov.: 35 AF XY: 0.000106 AC XY: 77AN XY: 727020
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2022 | This sequence change falls in intron 19 of the CCDC40 gene. It does not directly change the encoded amino acid sequence of the CCDC40 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs753716586, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. ClinVar contains an entry for this variant (Variation ID: 454890). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at