rs2041027
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_153676.4(USH1C):c.105-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,611,078 control chromosomes in the GnomAD database, including 138,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.42 ( 13292 hom., cov: 32)
Exomes 𝑓: 0.41 ( 125698 hom. )
Consequence
USH1C
NM_153676.4 splice_polypyrimidine_tract, intron
NM_153676.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.379
Genes affected
USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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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=-0.82).
BP6
?
Variant 11-17531558-G-A is Benign according to our data. Variant chr11-17531558-G-A is described in ClinVar as [Benign]. Clinvar id is 47972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17531558-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_005709.4 | c.105-16C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000318024.9 | |||
USH1C | NM_153676.4 | c.105-16C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000005226.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.105-16C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_153676.4 | ||||
USH1C | ENST00000318024.9 | c.105-16C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.417 AC: 63368AN: 151836Hom.: 13285 Cov.: 32
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GnomAD3 exomes AF: 0.420 AC: 104268AN: 248282Hom.: 22070 AF XY: 0.416 AC XY: 55952AN XY: 134356
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GnomAD4 exome AF: 0.413 AC: 602910AN: 1459122Hom.: 125698 Cov.: 56 AF XY: 0.411 AC XY: 298527AN XY: 725838
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GnomAD4 genome ? AF: 0.417 AC: 63392AN: 151956Hom.: 13292 Cov.: 32 AF XY: 0.417 AC XY: 30965AN XY: 74268
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 24, 2009 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 21, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 18A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Usher syndrome type 1C Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
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