chr10-20888214-G-GA
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_006393.3(NEBL):c.259-8_259-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,389,664 control chromosomes in the GnomAD database, including 1,471 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.085 ( 928 hom., cov: 31)
Exomes 𝑓: 0.012 ( 543 hom. )
Consequence
NEBL
NM_006393.3 splice_region, splice_polypyrimidine_tract, intron
NM_006393.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.367
Genes affected
NEBL (HGNC:16932): (nebulette) This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 10-20888214-G-GA is Benign according to our data. Variant chr10-20888214-G-GA is described in ClinVar as [Benign]. Clinvar id is 45495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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NEBL | NM_006393.3 | c.259-8_259-7insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.259-8_259-7insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes AF: 0.0853 AC: 9660AN: 113292Hom.: 925 Cov.: 31
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GnomAD3 exomes AF: 0.0222 AC: 4734AN: 213600Hom.: 265 AF XY: 0.0179 AC XY: 2069AN XY: 115848
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GnomAD4 exome AF: 0.0122 AC: 15621AN: 1276262Hom.: 543 Cov.: 23 AF XY: 0.0114 AC XY: 7283AN XY: 639522
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GnomAD4 genome AF: 0.0854 AC: 9685AN: 113402Hom.: 928 Cov.: 31 AF XY: 0.0847 AC XY: 4628AN XY: 54608
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 26, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 17, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 14, 2018 | c.259-8dup in intron 3 of NEBL: This variant is classified as benign because it has been identified in 23% (4831/20832) of African chromosomes by the Genome Agg regation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs753190853). ACMG/AMP Criteria: BA1. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
NEBL-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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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