rs876657543
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_001164507.2(NEB):c.13788+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NEB
NM_001164507.2 intron
NM_001164507.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.722
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 2-151600430-G-C is Benign according to our data. Variant chr2-151600430-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 227731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.13788+12C>G | intron_variant | ENST00000427231.7 | |||
NEB | NM_001164508.2 | c.13788+12C>G | intron_variant | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.13788+12C>G | intron_variant | 5 | NM_001164508.2 | P5 | |||
NEB | ENST00000427231.7 | c.13788+12C>G | intron_variant | 5 | NM_001164507.2 | A2 | |||
NEB | ENST00000409198.5 | c.11601+9379C>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.146 AC: 103AN: 706Hom.: 0 AF XY: 0.168 AC XY: 65AN XY: 388
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706
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 598Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 286
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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GnomAD4 genome ? Cov.: 0
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 19, 2014 | NEB exons 82-105 are organized in three repetitive blocks of 8 exons each and be cause these blocks are nearly identical in sequence, homologous exons (e.g., exo ns 82, 90, and 98) are co-amplified and sequenced (each amplicon consists of 6 a lleles). This variant represents a nonhomologous position within the three repet itive blocks (c.13788+12C, c.15246+12C, and c.16704+12G). The variable alleles a t this position are not expected to have clinical significance because these pos itions are not located within the splice consensus sequence. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 20, 2017 | 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. - |
Computational scores
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Name
Calibrated prediction
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Prediction
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