10-20888214-GAAA-GAA
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_006393.3(NEBL):c.259-8del 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 0.00259 in 1,403,682 control chromosomes in the GnomAD database, including 44 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 21 hom., cov: 31)
Exomes 𝑓: 0.0016 ( 23 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-GA-G is Benign according to our data. Variant chr10-20888214-GA-G is described in ClinVar as [Benign]. Clinvar id is 179196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20888214-GA-G is described in Lovd as [Likely_benign]. Variant chr10-20888214-GA-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (1544/113452) while in subpopulation AFR AF= 0.0403 (1381/34234). AF 95% confidence interval is 0.0386. There are 21 homozygotes in gnomad4. There are 751 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.259-8del | 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.259-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0136 AC: 1539AN: 113342Hom.: 21 Cov.: 31
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GnomAD3 exomes AF: 0.00256 AC: 546AN: 213600Hom.: 5 AF XY: 0.00201 AC XY: 233AN XY: 115848
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GnomAD4 exome AF: 0.00162 AC: 2096AN: 1290230Hom.: 23 Cov.: 23 AF XY: 0.00153 AC XY: 989AN XY: 646474
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GnomAD4 genome ? AF: 0.0136 AC: 1544AN: 113452Hom.: 21 Cov.: 31 AF XY: 0.0137 AC XY: 751AN XY: 54638
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 19, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 02, 2015 | 259-8delT in intron 3 of NEBL: This variant is located outside the conserved +/- 1, 2 region of the splicing consensus sequence, is part of a polyT stretch, and does not alter the sequence of the ROI. It has been identified in 3% (309/9414) of African Chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org/; dbSNP rs71578979). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 26, 2014 | 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. - |
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