rs575423101
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000377122.9(NEBL):c.2913C>T(p.Asp971=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,613,972 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 3 hom. )
Consequence
NEBL
ENST00000377122.9 synonymous
ENST00000377122.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.316
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 10-20785879-G-A is Benign according to our data. Variant chr10-20785879-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 164734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.316 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.2913C>T | p.Asp971= | synonymous_variant | 28/28 | ENST00000377122.9 | NP_006384.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.2913C>T | p.Asp971= | synonymous_variant | 28/28 | 1 | NM_006393.3 | ENSP00000366326 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000319 AC: 80AN: 250860Hom.: 0 AF XY: 0.000421 AC XY: 57AN XY: 135536
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GnomAD4 exome AF: 0.000144 AC: 210AN: 1461750Hom.: 3 Cov.: 31 AF XY: 0.000202 AC XY: 147AN XY: 727186
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GnomAD4 genome AF: 0.000145 AC: 22AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74424
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 09, 2013 | Asp971Asp in exon 28 of NEBL: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. Asp971Asp in exon 28 of NEBL (allele frequenc y = n/a) - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 19, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 03, 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