rs186902443
Variant names:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001164508.2(NEB):c.16788C>T(p.Asn5596Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,610,828 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 0.0011 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
NEB
NM_001164508.2 synonymous
NM_001164508.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.290
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=-0.47).
BP6
Variant 2-151576271-G-A is Benign according to our data. Variant chr2-151576271-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.29 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00114 (173/151388) while in subpopulation AFR AF= 0.00402 (166/41308). AF 95% confidence interval is 0.00352. There are 0 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NEB | ENST00000397345.8 | c.16788C>T | p.Asn5596Asn | synonymous_variant | Exon 106 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
| NEB | ENST00000427231.7 | c.16788C>T | p.Asn5596Asn | synonymous_variant | Exon 106 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
| NEB | ENST00000409198.5 | c.11685C>T | p.Asn3895Asn | synonymous_variant | Exon 79 of 150 | 5 | ENSP00000386259.1 | |||
| NEB | ENST00000413693.5 | c.978C>T | p.Asn326Asn | synonymous_variant | Exon 6 of 74 | 5 | ENSP00000410961.1 |
Frequencies
GnomAD3 genomes 0.00114 AC: 173AN: 151276Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000257 AC: 64AN: 248986Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 135080
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GnomAD4 exome AF: 0.0000932 AC: 136AN: 1459440Hom.: 0 Cov.: 30 AF XY: 0.0000689 AC XY: 50AN XY: 726048
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GnomAD4 genome 0.00114 AC: 173AN: 151388Hom.: 0 Cov.: 30 AF XY: 0.000906 AC XY: 67AN XY: 73980
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Mar 01, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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. -
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PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Nemaline myopathy 2 Benign:1
Nov 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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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