rs923819811
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_006393.3(NEBL):c.259-13T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,402,784 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006393.3 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.259-13T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.259-13T>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000732 AC: 7AN: 95648Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000124 AC: 2AN: 160850Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 87330
GnomAD4 exome AF: 0.00000995 AC: 13AN: 1307136Hom.: 0 Cov.: 20 AF XY: 0.00000759 AC XY: 5AN XY: 658598
GnomAD4 genome ? AF: 0.0000732 AC: 7AN: 95648Hom.: 0 Cov.: 30 AF XY: 0.0000432 AC XY: 2AN XY: 46246
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 15, 2017 | Variant classified as Uncertain Significance - Favor Benign. The c.259-13T>G var iant in NEBL has not been previously reported in individuals with cardiomyopathy . This variant has been identified in 2/17494 African chromosomes and 1/21470 La tin chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dnSNP rs 923819811). This variant is located in the 5' splice regi on. Computational tools do not suggest an impact to splicing. However, this info rmation is not predictive enough to rule out pathogenicity. In summary, the cli nical significance of the c.259-13T>G variant is uncertain. ACMG/AMP Criteria ap plied: PM2; BP4. - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at