chr10-84194821-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033100.4(CDHR1):c.55+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 0.0000263 in 152,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Consequence
CDHR1
NM_033100.4 splice_donor_region, intron
NM_033100.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.04567
2
Clinical Significance
Conservation
PhyloP100: 0.704
Genes affected
CDHR1 (HGNC:14550): (cadherin related family member 1) This gene belongs to the cadherin superfamily of calcium-dependent cell adhesion molecules. The encoded protein is a photoreceptor-specific cadherin that plays a role in outer segment disc morphogenesis. Mutations in this gene are associated with inherited retinal dystrophies. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDHR1 | NM_033100.4 | c.55+6T>C | splice_donor_region_variant, intron_variant | ENST00000623527.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDHR1 | ENST00000623527.4 | c.55+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_033100.4 | P2 | |||
CDHR1 | ENST00000332904.7 | c.55+6T>C | splice_donor_region_variant, intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152012Hom.: 0 Cov.: 33
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GnomAD4 exome Cov.: 31
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152012Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74260
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 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 create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1360921). This variant has not been reported in the literature in individuals affected with CDHR1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -47
Find out detailed SpliceAI scores and Pangolin per-transcript scores at