rs75977878
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The ENST00000318024.9(USH1C):āc.651A>Gā(p.Val217=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,614,004 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.024 ( 151 hom., cov: 33)
Exomes š: 0.0027 ( 138 hom. )
Consequence
USH1C
ENST00000318024.9 synonymous
ENST00000318024.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0130
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 11-17526370-T-C is Benign according to our data. Variant chr11-17526370-T-C is described in ClinVar as [Benign]. Clinvar id is 48021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.013 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.651A>G | p.Val217= | synonymous_variant | 8/27 | ENST00000005226.12 | NP_710142.1 | |
USH1C | NM_005709.4 | c.651A>G | p.Val217= | synonymous_variant | 8/21 | ENST00000318024.9 | NP_005700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.651A>G | p.Val217= | synonymous_variant | 8/27 | 5 | NM_153676.4 | ENSP00000005226 | ||
USH1C | ENST00000318024.9 | c.651A>G | p.Val217= | synonymous_variant | 8/21 | 1 | NM_005709.4 | ENSP00000317018 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0238 AC: 3628AN: 152172Hom.: 150 Cov.: 33
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GnomAD3 exomes AF: 0.00657 AC: 1650AN: 251146Hom.: 71 AF XY: 0.00506 AC XY: 687AN XY: 135778
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GnomAD4 exome AF: 0.00271 AC: 3963AN: 1461714Hom.: 138 Cov.: 32 AF XY: 0.00241 AC XY: 1756AN XY: 727160
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GnomAD4 genome AF: 0.0239 AC: 3635AN: 152290Hom.: 151 Cov.: 33 AF XY: 0.0238 AC XY: 1769AN XY: 74452
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 28, 2011 | Val217Val in exon 8 of USH1C: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located near a splice junction and is found in over 1% of cases. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 02, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Usher syndrome type 1C Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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