rs116339167
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033056.4(PCDH15):c.877-29G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,526,374 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 33 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 52 hom. )
Consequence
PCDH15
NM_033056.4 intron
NM_033056.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.538
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=-0.86).
BP6
?
Variant 10-54236960-C-A is Benign according to our data. Variant chr10-54236960-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 262151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-54236960-C-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2186/152152) while in subpopulation AFR AF= 0.0448 (1859/41518). AF 95% confidence interval is 0.0431. There are 33 homozygotes in gnomad4. There are 1019 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 33 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH15 | NM_001384140.1 | c.877-29G>T | intron_variant | ENST00000644397.2 | |||
PCDH15 | NM_033056.4 | c.877-29G>T | intron_variant | ENST00000320301.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.877-29G>T | intron_variant | 1 | NM_033056.4 | ||||
PCDH15 | ENST00000644397.2 | c.877-29G>T | intron_variant | NM_001384140.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0144 AC: 2184AN: 152034Hom.: 33 Cov.: 33
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GnomAD3 exomes AF: 0.00492 AC: 1235AN: 251146Hom.: 23 AF XY: 0.00402 AC XY: 546AN XY: 135742
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GnomAD4 exome AF: 0.00267 AC: 3664AN: 1374222Hom.: 52 Cov.: 23 AF XY: 0.00251 AC XY: 1729AN XY: 689182
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GnomAD4 genome ? AF: 0.0144 AC: 2186AN: 152152Hom.: 33 Cov.: 33 AF XY: 0.0137 AC XY: 1019AN XY: 74400
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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 specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at