rs2296610
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006393.3(NEBL):c.656C>A(p.Ala219Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00787 in 1,611,660 control chromosomes in the GnomAD database, including 673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A219T) has been classified as Uncertain significance.
Frequency
Consequence
NM_006393.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.656C>A | p.Ala219Asp | missense_variant | 7/28 | ENST00000377122.9 | |
LOC102725112 | XR_007062082.1 | n.351+3225G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.656C>A | p.Ala219Asp | missense_variant | 7/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0126 AC: 1916AN: 152022Hom.: 97 Cov.: 32
GnomAD3 exomes AF: 0.0199 AC: 4988AN: 251144Hom.: 279 AF XY: 0.0184 AC XY: 2497AN XY: 135724
GnomAD4 exome AF: 0.00738 AC: 10775AN: 1459520Hom.: 577 Cov.: 31 AF XY: 0.00719 AC XY: 5219AN XY: 726252
GnomAD4 genome ? AF: 0.0126 AC: 1911AN: 152140Hom.: 96 Cov.: 32 AF XY: 0.0166 AC XY: 1237AN XY: 74380
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 10, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Ala219Asp in Exon 07 of NEBL: This variant is not expected to have clinical si gnificance because it has been identified in 20.7% (17/82) of chromosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs2 296610). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
NEBL-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 02, 2013 | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at