rs200889109
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_153676.4(USH1C):c.2184+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,614,014 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 1 hom. )
Consequence
USH1C
NM_153676.4 intron
NM_153676.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.517
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 -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 11-17504637-A-G is Benign according to our data. Variant chr11-17504637-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 178565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17504637-A-G is described in Lovd as [Benign]. Variant chr11-17504637-A-G is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_005709.4 | c.1285-2657T>C | intron_variant | ENST00000318024.9 | |||
USH1C | NM_153676.4 | c.2184+10T>C | intron_variant | ENST00000005226.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.2184+10T>C | intron_variant | 5 | NM_153676.4 | ||||
USH1C | ENST00000318024.9 | c.1285-2657T>C | intron_variant | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000717 AC: 109AN: 152126Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000215 AC: 54AN: 251450Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135900
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GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461770Hom.: 1 Cov.: 31 AF XY: 0.0000564 AC XY: 41AN XY: 727198
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GnomAD4 genome ? AF: 0.000723 AC: 110AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.000793 AC XY: 59AN XY: 74434
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 2184+10T>C in Intron 20 of USH1C: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 0.3% (10/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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