rs182725059
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001164507.2(NEB):āc.3801T>Cā(p.Asp1267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,584,466 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00096 ( 1 hom., cov: 32)
Exomes š: 0.000084 ( 0 hom. )
Consequence
NEB
NM_001164507.2 synonymous
NM_001164507.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.646
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 -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 2-151675365-A-G is Benign according to our data. Variant chr2-151675365-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 389565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151675365-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.646 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000958 (146/152346) while in subpopulation AFR AF= 0.00339 (141/41578). AF 95% confidence interval is 0.00293. There are 1 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.3801T>C | p.Asp1267= | synonymous_variant | 35/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.3801T>C | p.Asp1267= | synonymous_variant | 35/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.3801T>C | p.Asp1267= | synonymous_variant | 35/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.3801T>C | p.Asp1267= | synonymous_variant | 35/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.3801T>C | p.Asp1267= | synonymous_variant | 35/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000946 AC: 144AN: 152228Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000234 AC: 48AN: 205012Hom.: 1 AF XY: 0.000174 AC XY: 19AN XY: 109226
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GnomAD4 exome AF: 0.0000838 AC: 120AN: 1432120Hom.: 0 Cov.: 30 AF XY: 0.0000705 AC XY: 50AN XY: 709526
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GnomAD4 genome ? AF: 0.000958 AC: 146AN: 152346Hom.: 1 Cov.: 32 AF XY: 0.000792 AC XY: 59AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2021 | - - |
Nemaline myopathy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at