ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.274G>C (p.Glu92Gln)

gnomAD frequency: 0.00029  dbSNP: rs146651027
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186963 SCV000240534 benign not specified 2017-10-03 criteria provided, single submitter clinical testing 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.
Invitae RCV000654308 SCV000776198 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2024-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002314694 SCV000849052 likely benign Inborn genetic diseases 2018-08-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767933 SCV000898609 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 1 2018-08-27 criteria provided, single submitter clinical testing CHRNA4 NM_000744.6 exon 4 c.274G>A (p.Glu92Gln): This variant has not been reported in the literature and is present in 0.06% (75/119670) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/20-61987436-C-G). This variant is present in ClinVar (Variation ID:205043). Evolutionary conservation of this residue suggests that this may impact the protein, but computational predictive tools for this variant are conflicting. Of note, computational tools designed to predict splicing suggest a potential effect from this variant. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen RCV001090874 SCV001246636 likely benign not provided 2022-07-01 criteria provided, single submitter clinical testing CHRNA4: PP3, BS1
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000477750 SCV003919799 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 1; Tobacco addiction, susceptibility to 2021-11-11 criteria provided, single submitter clinical testing CHRNA4 NM_000744.6 exon 4 c.274G>A (p.Glu92Gln): This variant has not been reported in the literature and is present in 0.06% (75/119670) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/20-61987436-C-G). This variant is present in ClinVar (Variation ID:205043). Evolutionary conservation of this residue suggests that this may impact the protein, but computational predictive tools for this variant are conflicting. Of note, computational tools designed to predict splicing suggest a potential effect from this variant. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences RCV003947567 SCV004763863 likely benign CHRNA4-related condition 2023-02-07 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Division of Human Genetics, Children's Hospital of Philadelphia RCV000477750 SCV000536811 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 1; Tobacco addiction, susceptibility to 2016-07-03 no assertion criteria provided research

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