rs372976809
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017950.4(CCDC40):c.1372G>A(p.Ala458Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,614,160 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_017950.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.1372G>A | p.Ala458Thr | missense_variant | Exon 9 of 20 | ENST00000397545.9 | NP_060420.2 | |
CCDC40 | NM_001243342.2 | c.1372G>A | p.Ala458Thr | missense_variant | Exon 9 of 18 | NP_001230271.1 | ||
CCDC40 | NM_001330508.2 | c.1372G>A | p.Ala458Thr | missense_variant | Exon 9 of 11 | NP_001317437.1 | ||
LOC124904074 | XR_007065931.1 | n.879C>T | non_coding_transcript_exon_variant | Exon 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152162Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00155 AC: 388AN: 249588Hom.: 6 AF XY: 0.00215 AC XY: 291AN XY: 135410
GnomAD4 exome AF: 0.000754 AC: 1102AN: 1461882Hom.: 16 Cov.: 32 AF XY: 0.00107 AC XY: 777AN XY: 727240
GnomAD4 genome AF: 0.000381 AC: 58AN: 152278Hom.: 1 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74454
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
This alteration is classified as likely 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. -
- -
Primary ciliary dyskinesia 15 Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at