rs144946187
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_006393.3(NEBL):c.2964C>T(p.Asp988=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )
Consequence
NEBL
NM_006393.3 synonymous
NM_006393.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.325
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 10-20785828-G-A is Benign according to our data. Variant chr10-20785828-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 392612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20785828-G-A is described in Lovd as [Likely_benign].
BP7
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Synonymous conserved (PhyloP=-0.325 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.2964C>T | p.Asp988= | synonymous_variant | 28/28 | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.2964C>T | p.Asp988= | synonymous_variant | 28/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000199 AC: 50AN: 250968Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135608
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GnomAD4 exome AF: 0.000279 AC: 408AN: 1461738Hom.: 0 Cov.: 31 AF XY: 0.000270 AC XY: 196AN XY: 727168
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GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74294
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ClinVar
Significance: Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | NEBL: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2022 | This alteration is classified as likely 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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