2-151618284-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting
The NM_001164507.2(NEB):c.11067C>T(p.Asn3689=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,613,674 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 2 hom. )
Consequence
NEB
NM_001164507.2 synonymous
NM_001164507.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.92
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 2-151618284-G-A is Benign according to our data. Variant chr2-151618284-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 389787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.92 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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NEB | NM_001164507.2 | c.11067C>T | p.Asn3689= | synonymous_variant | 74/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.11067C>T | p.Asn3689= | synonymous_variant | 74/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.11067C>T | p.Asn3689= | synonymous_variant | 74/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.11067C>T | p.Asn3689= | synonymous_variant | 74/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.10338C>T | p.Asn3446= | synonymous_variant | 71/150 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000427 AC: 65AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000450 AC: 112AN: 248706Hom.: 0 AF XY: 0.000511 AC XY: 69AN XY: 134914
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GnomAD4 exome AF: 0.000631 AC: 922AN: 1461502Hom.: 2 Cov.: 31 AF XY: 0.000615 AC XY: 447AN XY: 727072
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GnomAD4 genome AF: 0.000427 AC: 65AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.000538 AC XY: 40AN XY: 74332
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | NEB: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 22, 2020 | - - |
NEB-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 15, 2019 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at