chr15-43610931-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_153700.2(STRC):āc.3360T>Cā(p.Cys1120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 146,078 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.019 ( 86 hom., cov: 22)
Exomes š: 0.011 ( 2718 hom. )
Failed GnomAD Quality Control
Consequence
STRC
NM_153700.2 synonymous
NM_153700.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.191
Genes affected
STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]
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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=-0.82).
BP6
Variant 15-43610931-A-G is Benign according to our data. Variant chr15-43610931-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 227082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43610931-A-G is described in Lovd as [Benign]. Variant chr15-43610931-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.191 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2784/146078) while in subpopulation NFE AF= 0.031 (1996/64330). AF 95% confidence interval is 0.0299. There are 86 homozygotes in gnomad4. There are 1325 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 86 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.3360T>C | p.Cys1120= | synonymous_variant | 14/29 | ENST00000450892.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.3360T>C | p.Cys1120= | synonymous_variant | 14/29 | 5 | NM_153700.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0191 AC: 2787AN: 145958Hom.: 86 Cov.: 22
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GnomAD3 exomes AF: 0.0133 AC: 3179AN: 238230Hom.: 326 AF XY: 0.0132 AC XY: 1690AN XY: 128488
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0111 AC: 15335AN: 1381298Hom.: 2718 Cov.: 29 AF XY: 0.0112 AC XY: 7682AN XY: 688280
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.0191 AC: 2784AN: 146078Hom.: 86 Cov.: 22 AF XY: 0.0185 AC XY: 1325AN XY: 71594
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
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 26, 2013 | Cys1120Cys in Exon 14 of STRC: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 7.6% (10/132) of chromoso mes from an European American (CEU) population in 1000Genomes project (reported in Deafness Variation Database: http://deafnessvariationdatabase.org; dbSNP rs56 385906). - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2019 | - - |
Autosomal recessive nonsyndromic hearing loss 16 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
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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