rs377648518
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The ENST00000417816.2(NEBL):c.69+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000912 in 1,612,548 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 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000090 ( 0 hom. )
Consequence
NEBL
ENST00000417816.2 intron
ENST00000417816.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.440
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 10-21173750-C-A is Benign according to our data. Variant chr10-21173750-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 164778.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_001377324.1 | c.-75G>T | 5_prime_UTR_variant | 1/7 | |||
NEBL | NM_001173484.2 | c.69+15G>T | intron_variant | ||||
NEBL | NM_001377322.1 | c.69+15G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000417816.2 | c.69+15G>T | intron_variant | 1 | P1 | ||||
NEBL | ENST00000464278.1 | n.74+15G>T | intron_variant, non_coding_transcript_variant | 3 | |||||
NEBL | ENST00000675700.1 | n.92+1090G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000162 AC: 40AN: 247306Hom.: 0 AF XY: 0.000164 AC XY: 22AN XY: 134292
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GnomAD4 exome AF: 0.0000897 AC: 131AN: 1460448Hom.: 0 Cov.: 32 AF XY: 0.0000908 AC XY: 66AN XY: 726588
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74294
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | 69+15G>T in intron 1 of NEBL: This variant is not expected to have clinical sign ificance because it is not located within the splice consensus sequence. It has been identified in 2/7020 European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). 69+15 G>T in intron 1 of NEBL (allele frequency = 2/7020) ** - |
Computational scores
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BayesDel_noAF
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CADD
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at