rs1006363
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006393.3(NEBL):c.2031G>A(p.Arg677=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,702 control chromosomes in the GnomAD database, including 66,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.22 ( 4653 hom., cov: 32)
Exomes 𝑓: 0.28 ( 61714 hom. )
Consequence
NEBL
NM_006393.3 synonymous
NM_006393.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0920
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 10-20819448-C-T is Benign according to our data. Variant chr10-20819448-C-T is described in ClinVar as [Benign]. Clinvar id is 45489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.092 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.2031G>A | p.Arg677= | synonymous_variant | 20/28 | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.2031G>A | p.Arg677= | synonymous_variant | 20/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.223 AC: 33874AN: 151958Hom.: 4653 Cov.: 32
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GnomAD3 exomes AF: 0.247 AC: 62107AN: 251314Hom.: 8586 AF XY: 0.250 AC XY: 33907AN XY: 135824
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GnomAD4 exome AF: 0.284 AC: 414474AN: 1461626Hom.: 61714 Cov.: 37 AF XY: 0.281 AC XY: 204568AN XY: 727142
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GnomAD4 genome ? AF: 0.223 AC: 33870AN: 152076Hom.: 4653 Cov.: 32 AF XY: 0.226 AC XY: 16784AN XY: 74348
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 09, 2013 | 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 04, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Arg677Arg in Exon 20 of NEBL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence and has been identified in 29.6% (2079/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1006363). - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 22, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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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