rs111033477
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2
The NM_000260.4(MYO7A):c.5215C>A(p.Arg1739=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0013 in 1,549,206 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00069 ( 13 hom. )
Consequence
MYO7A
NM_000260.4 synonymous
NM_000260.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.64
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.13).
BP6
?
Variant 11-77203106-C-A is Benign according to our data. Variant chr11-77203106-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 43276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77203106-C-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1048/152312) while in subpopulation AFR AF= 0.0239 (995/41572). AF 95% confidence interval is 0.0227. There are 6 homozygotes in gnomad4. There are 483 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.5215C>A | p.Arg1739= | synonymous_variant | 38/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.5215C>A | p.Arg1739= | synonymous_variant | 38/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00687 AC: 1045AN: 152194Hom.: 6 Cov.: 33
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GnomAD3 exomes AF: 0.00135 AC: 207AN: 153198Hom.: 3 AF XY: 0.00104 AC XY: 85AN XY: 81544
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GnomAD4 exome AF: 0.000692 AC: 966AN: 1396894Hom.: 13 Cov.: 31 AF XY: 0.000591 AC XY: 407AN XY: 689064
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GnomAD4 genome ? AF: 0.00688 AC: 1048AN: 152312Hom.: 6 Cov.: 33 AF XY: 0.00649 AC XY: 483AN XY: 74470
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 26, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 28, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 06, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 03, 2011 | Arg1739Arg in exon 38 of MYO7A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located near a splice junction and has been identified in 2.9% (13/452 chromosomes) of a broa d population (dbSNP rs111033477). - |
Autosomal recessive nonsyndromic hearing loss 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Autosomal dominant nonsyndromic hearing loss 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Usher syndrome type 1B Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 06, 2019 | - - |
Usher syndrome type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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Name
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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