rs111033223
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000260.4(MYO7A):c.3503+12_3503+33del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,578,114 control chromosomes in the GnomAD database, including 170,662 homozygotes. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.45 ( 16051 hom., cov: 0)
Exomes 𝑓: 0.46 ( 154611 hom. )
Consequence
MYO7A
NM_000260.4 intron
NM_000260.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.09
Genes affected
MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 11-77184725-GGGAGGCGGGGACACCAGGGCCT-G is Benign according to our data. Variant chr11-77184725-GGGAGGCGGGGACACCAGGGCCT-G is described in ClinVar as [Benign]. Clinvar id is 43207.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr11-77184725-GGGAGGCGGGGACACCAGGGCCT-G is described in Lovd as [Benign]. Variant chr11-77184725-GGGAGGCGGGGACACCAGGGCCT-G is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.3503+12_3503+33del | intron_variant | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3503+12_3503+33del | intron_variant | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.455 AC: 69092AN: 151924Hom.: 16041 Cov.: 0
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GnomAD3 exomes AF: 0.380 AC: 76594AN: 201658Hom.: 16257 AF XY: 0.368 AC XY: 40024AN XY: 108766
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GnomAD4 exome AF: 0.456 AC: 649803AN: 1426072Hom.: 154611 AF XY: 0.449 AC XY: 317982AN XY: 707850
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GnomAD4 genome ? AF: 0.455 AC: 69133AN: 152042Hom.: 16051 Cov.: 0 AF XY: 0.456 AC XY: 33879AN XY: 74326
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 19, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 05, 2012 | See NM_000260 c.3503+12_3503+33del - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2013 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 07, 2023 | - - |
Autosomal recessive nonsyndromic hearing loss 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Usher syndrome type 1B Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 25, 2019 | - - |
Nonsyndromic genetic hearing loss Benign:1
Benign, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | Sep 28, 2018 | The filtering allele frequency of the c.3503+12_3503+33del (p.Gly1172GlufsX34) variant in the MYO7A gene is 50.8% (11084/21494) of European (Finnish) chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Usher syndrome type 1;C1832475:Autosomal dominant nonsyndromic hearing loss 11;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 11, 2021 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at