rs121908338
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001368067.1(LDB3):c.349G>A(p.Asp117Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00376 in 1,613,780 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D117H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001368067.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDB3 | NM_001368067.1 | c.349G>A | p.Asp117Asn | missense_variant | 6/9 | ENST00000263066.11 | |
LDB3 | NM_007078.3 | c.690-4823G>A | intron_variant | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000263066.11 | c.349G>A | p.Asp117Asn | missense_variant | 6/9 | 1 | NM_001368067.1 | ||
LDB3 | ENST00000361373.9 | c.690-4823G>A | intron_variant | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00710 AC: 1079AN: 151984Hom.: 8 Cov.: 33
GnomAD3 exomes AF: 0.00450 AC: 1122AN: 249184Hom.: 6 AF XY: 0.00457 AC XY: 618AN XY: 135214
GnomAD4 exome AF: 0.00342 AC: 4996AN: 1461678Hom.: 31 Cov.: 33 AF XY: 0.00356 AC XY: 2586AN XY: 727106
GnomAD4 genome ? AF: 0.00708 AC: 1077AN: 152102Hom.: 8 Cov.: 33 AF XY: 0.00695 AC XY: 517AN XY: 74350
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 23, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 02, 2020 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 07, 2013 | Asp117Asn in exon 6 of LDB3: This variant is not expected to have clinical signi ficance because it has been identified in 1.3% (51/4090) of African American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e vs.gs.washington.edu/EVS; dbSNP rs121908338). It has been reported in 2 individu als with DCM and 1 individual with LVNC (Vatta 2002, Xi 2012). In vitro studies suggest that it may have functional consequences (Xi 2012), though it should be noted that in vitro studies may not accurately represent biological function and /or may not translate to disease. In summary, the frequency of this variant in the general population suggests that it does not cause disease on its own. It re mains possible that it modifies disease expression. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:7
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2018 | This variant is associated with the following publications: (PMID: 14662268, 26636822, 26419279, 28416588, 22929165, 23299917, 22995991, 22619057, 27884173, 27896284, 30293248, 30972196, 25214167) - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 01, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | LDB3: BP4, BS1, BS2 - |
Dilated cardiomyopathy 1C Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Uncertain significance, no assertion criteria provided | literature only | OMIM | Dec 03, 2003 | - - |
Primary dilated cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Feb 28, 2017 | - - |
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Myofibrillar myopathy 4 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 | Jan 11, 2016 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at