rs781520817
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001164507.2(NEB):c.22273-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 1,343,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000060 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
NEB
NM_001164507.2 splice_polypyrimidine_tract, intron
NM_001164507.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0007861
2
Clinical Significance
Conservation
PhyloP100: 0.123
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 2-151524626-G-A is Benign according to our data. Variant chr2-151524626-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 534048.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.22273-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000427231.7 | |||
NEB | NM_001164508.2 | c.22273-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.22273-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001164508.2 | P5 | |||
NEB | ENST00000427231.7 | c.22273-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000602 AC: 9AN: 149586Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000567 AC: 14AN: 246802Hom.: 0 AF XY: 0.0000523 AC XY: 7AN XY: 133970
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GnomAD4 exome AF: 0.0000771 AC: 92AN: 1193502Hom.: 0 Cov.: 29 AF XY: 0.0000729 AC XY: 44AN XY: 603524
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GnomAD4 genome ? AF: 0.0000602 AC: 9AN: 149586Hom.: 0 Cov.: 31 AF XY: 0.0000412 AC XY: 3AN XY: 72860
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nemaline myopathy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at