rs199524735
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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.3540T>Gā(p.Leu1180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,608,722 control chromosomes in the GnomAD database, including 66 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 0.0034 ( 23 hom., cov: 26)
Exomes š: 0.00076 ( 43 hom. )
Consequence
STRC
NM_153700.2 synonymous
NM_153700.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.275
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=-0.68).
BP6
?
Variant 15-43609293-A-C is Benign according to our data. Variant chr15-43609293-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 227965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43609293-A-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.275 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0034 (511/150282) while in subpopulation AFR AF= 0.00737 (294/39892). AF 95% confidence interval is 0.00668. There are 23 homozygotes in gnomad4. There are 267 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRC | NM_153700.2 | c.3540T>G | p.Leu1180= | synonymous_variant | 16/29 | ENST00000450892.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRC | ENST00000450892.7 | c.3540T>G | p.Leu1180= | synonymous_variant | 16/29 | 5 | NM_153700.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00341 AC: 512AN: 150168Hom.: 23 Cov.: 26
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GnomAD3 exomes AF: 0.000859 AC: 215AN: 250252Hom.: 15 AF XY: 0.000857 AC XY: 116AN XY: 135300
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GnomAD4 exome AF: 0.000762 AC: 1112AN: 1458440Hom.: 43 Cov.: 31 AF XY: 0.000926 AC XY: 672AN XY: 725552
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GnomAD4 genome ? AF: 0.00340 AC: 511AN: 150282Hom.: 23 Cov.: 26 AF XY: 0.00363 AC XY: 267AN XY: 73478
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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:3
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The STRC p.Leu1180Leu variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs199524735) and in ClinVar (classified as benign by Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine). The variant was also identified in control databases in 284 of 281132 chromosomes (20 homozygous) at a frequency of 0.00101 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017) and was observed in the following populations: African in 98 of 24194 chromosomes (freq: 0.004051), South Asian in 58 of 30480 chromosomes (freq: 0.001903), Latino in 58 of 35362 chromosomes (freq: 0.00164), East Asian in 14 of 19680 chromosomes (freq: 0.000711), Other in 4 of 7204 chromosomes (freq: 0.000555), Ashkenazi Jewish in 5 of 10354 chromosomes (freq: 0.000483), European (non-Finnish) in 44 of 128746 chromosomes (freq: 0.000342), and European (Finnish) in 3 of 25112 chromosomes (freq: 0.00012). The p.Leu1180Leu variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. Three in silico or computational prediction software programs (MaxEntScan, NNSPLICE, GeneSplicer) predict the loss of an unannotated 5' splice site, however the known canonical splice site is not predicted to be affected. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 20, 2017 | p.Leu1180Leu in exon 16 of STRC: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and it has been identified in 0.4% (97/23254) African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org; dbSNP rs199524735). - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 22, 2020 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | STRC: BP4, BP7, BS2 - |
Autosomal recessive nonsyndromic hearing loss 16 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
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