10-84194820-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_033100.4(CDHR1):c.55+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000783 in 1,532,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033100.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDHR1 | NM_033100.4 | c.55+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000623527.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDHR1 | ENST00000623527.4 | c.55+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_033100.4 | P2 | |||
CDHR1 | ENST00000332904.7 | c.55+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000233 AC: 3AN: 128968Hom.: 0 AF XY: 0.0000426 AC XY: 3AN XY: 70402
GnomAD4 exome AF: 0.00000797 AC: 11AN: 1380736Hom.: 0 Cov.: 31 AF XY: 0.0000117 AC XY: 8AN XY: 681390
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | 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. 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 may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1481982). This variant has not been reported in the literature in individuals affected with CDHR1-related conditions. This variant is present in population databases (rs777630035, gnomAD 0.004%). This sequence change falls in intron 1 of the CDHR1 gene. It does not directly change the encoded amino acid sequence of the CDHR1 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at