rs200249470
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_006393.3(NEBL):c.369+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,580,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006393.3 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.369+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.369+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152018Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251292Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135822
GnomAD4 exome AF: 0.000181 AC: 259AN: 1428358Hom.: 0 Cov.: 28 AF XY: 0.000187 AC XY: 133AN XY: 712950
GnomAD4 genome AF: 0.000184 AC: 28AN: 152018Hom.: 0 Cov.: 33 AF XY: 0.000162 AC XY: 12AN XY: 74238
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 | Jul 03, 2014 | The 369+5G>A variant in NEBL has not been previously reported in individuals wit h cardiomyopathy, but has been identified in 4/8600 of European American chromos omes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; d bSNP rs200249470). This variant is located in the 5' splice region. Computationa l tools suggest an impact to splicing, but this information is not predictive en ough to determine pathogenicity. In summary, the clinical significance of the 36 9+5G>A variant is uncertain. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 11, 2021 | - - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at