rs536400111
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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):āc.27A>Cā(p.Ile9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,605,464 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 (ā ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00022 ( 0 hom. )
Consequence
NEBL
NM_006393.3 synonymous
NM_006393.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.441
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=-0.82).
BP6
?
Variant 10-20897179-T-G is Benign according to our data. Variant chr10-20897179-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 240650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.441 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.27A>C | p.Ile9= | synonymous_variant | 1/28 | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.27A>C | p.Ile9= | synonymous_variant | 1/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152234Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000257 AC: 62AN: 241250Hom.: 0 AF XY: 0.000261 AC XY: 34AN XY: 130436
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GnomAD4 exome AF: 0.000217 AC: 315AN: 1453230Hom.: 0 Cov.: 31 AF XY: 0.000217 AC XY: 157AN XY: 722858
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74382
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2019 | - - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2023 | - - |
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