rs77290854
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033056.4(PCDH15):c.92-493A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,568,094 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0082 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00083 ( 19 hom. )
Consequence
PCDH15
NM_033056.4 intron
NM_033056.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.293
Genes affected
PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]
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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=-0.6).
BP6
?
Variant 10-54528370-T-A is Benign according to our data. Variant chr10-54528370-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 445899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-54528370-T-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00823 (1252/152134) while in subpopulation AFR AF= 0.0284 (1180/41554). AF 95% confidence interval is 0.0271. There are 16 homozygotes in gnomad4. There are 578 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 16 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH15 | NM_001384140.1 | c.92-493A>T | intron_variant | ENST00000644397.2 | |||
PCDH15 | NM_033056.4 | c.92-493A>T | intron_variant | ENST00000320301.11 | |||
LOC105378311 | NR_134503.1 | n.88-40195T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.92-493A>T | intron_variant | 1 | NM_033056.4 | ||||
PCDH15 | ENST00000644397.2 | c.92-493A>T | intron_variant | NM_001384140.1 | |||||
ENST00000422842.1 | n.88-40195T>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00822 AC: 1250AN: 152016Hom.: 16 Cov.: 32
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GnomAD3 exomes AF: 0.00197 AC: 379AN: 192076Hom.: 6 AF XY: 0.00161 AC XY: 165AN XY: 102308
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GnomAD4 exome AF: 0.000833 AC: 1179AN: 1415960Hom.: 19 Cov.: 30 AF XY: 0.000728 AC XY: 510AN XY: 701008
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GnomAD4 genome ? AF: 0.00823 AC: 1252AN: 152134Hom.: 16 Cov.: 32 AF XY: 0.00777 AC XY: 578AN XY: 74384
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 14, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 11, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at