rs772001300
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1
The NM_001164507.2(NEB):c.23649+10_23649+11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000891 in 1,594,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000091 ( 0 hom. )
Consequence
NEB
NM_001164507.2 intron
NM_001164507.2 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.216
Genes affected
NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]
RIF1 (HGNC:23207): (replication timing regulatory factor 1) This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 2-151506154-CTG-C is Benign according to our data. Variant chr2-151506154-CTG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211585.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=1}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000908 (131/1442206) while in subpopulation AMR AF= 0.00284 (127/44702). AF 95% confidence interval is 0.00244. There are 0 homozygotes in gnomad4_exome. There are 54 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.23649+10_23649+11del | intron_variant | ENST00000427231.7 | |||
NEB | NM_001164508.2 | c.23649+10_23649+11del | intron_variant | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.23649+10_23649+11del | intron_variant | 5 | NM_001164508.2 | P5 | |||
NEB | ENST00000427231.7 | c.23649+10_23649+11del | intron_variant | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000462 AC: 115AN: 249140Hom.: 0 AF XY: 0.000333 AC XY: 45AN XY: 135146
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GnomAD4 exome AF: 0.0000908 AC: 131AN: 1442206Hom.: 0 AF XY: 0.0000751 AC XY: 54AN XY: 718668
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74362
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 25, 2014 | - - |
NEB-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 13, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Nemaline myopathy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at