rs78226234
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001164507.2(NEB):c.7644+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,569,952 control chromosomes in the GnomAD database, including 343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.012 ( 18 hom., cov: 32)
Exomes 𝑓: 0.018 ( 325 hom. )
Consequence
NEB
NM_001164507.2 intron
NM_001164507.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.733
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=-0.92).
BP6
?
Variant 2-151644443-A-G is Benign according to our data. Variant chr2-151644443-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257831.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-151644443-A-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0122 (1861/152296) while in subpopulation SAS AF= 0.0317 (153/4824). AF 95% confidence interval is 0.0276. There are 18 homozygotes in gnomad4. There are 876 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 18 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.7644+25T>C | intron_variant | ENST00000427231.7 | |||
NEB | NM_001164508.2 | c.7644+25T>C | intron_variant | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.7644+25T>C | intron_variant | 5 | NM_001164508.2 | P5 | |||
NEB | ENST00000427231.7 | c.7644+25T>C | intron_variant | 5 | NM_001164507.2 | A2 | |||
NEB | ENST00000409198.5 | c.7644+25T>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0122 AC: 1863AN: 152178Hom.: 18 Cov.: 32
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GnomAD3 exomes AF: 0.0147 AC: 3655AN: 247888Hom.: 59 AF XY: 0.0159 AC XY: 2136AN XY: 134452
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GnomAD4 exome AF: 0.0183 AC: 25969AN: 1417656Hom.: 325 Cov.: 27 AF XY: 0.0186 AC XY: 13157AN XY: 707792
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GnomAD4 genome ? AF: 0.0122 AC: 1861AN: 152296Hom.: 18 Cov.: 32 AF XY: 0.0118 AC XY: 876AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
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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