Submissions for variant NM_000744.7(CHRNA4):c.1460G>A (p.Arg487Gln)

gnomAD frequency: 0.00152  dbSNP: rs121912280

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001529471	SCV000240520	benign	not provided	2020-12-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19628475, 21107856, 24385388, 22873564, 29422393)
Eurofins Ntd Llc (ga)	RCV000186949	SCV000331400	benign	not specified	2015-10-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000528520	SCV000658073	benign	Autosomal dominant nocturnal frontal lobe epilepsy	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316284	SCV000849682	likely benign	Inborn genetic diseases	2018-11-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000767931	SCV000898607	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 1	2017-10-26	criteria provided, single submitter	clinical testing	CHRNA4 NM_000744.6 exon 5 p.Arg487Gln (c.1460G>A): This variant has been reported in the literature in 1 individual with Sporadic Amyotrophic Lateral Sclerosis (SALS) (Sabatelli 2009 PMID:19628475). This variant is present in 0.4% (85/1944) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs121912280). This variant Glutamine (Gln) is present in >5 species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224145	SCV003919796	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 1; Tobacco addiction, susceptibility to	2021-03-30	criteria provided, single submitter	clinical testing	CHRNA4 NM_000744 exon 5 p.Arg487Gln (c.1460G>A): This variant has been reported in the literature in 1 individual with Sporadic Amyotrophic Lateral Sclerosis (SALS) (Sabatelli 2009 PMID:19628475). This variant is present in 0.4% (85/1944) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs121912280). This variant Glutamine (Gln) is present in >5 species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an 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	RCV001529471	SCV004150889	benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	CHRNA4: BS1, BS2
Psychiatry Genetics Yale University	RCV000084608	SCV000116744	not provided	Tobacco use disorder		no assertion provided	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529471	SCV001742986	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529471	SCV001932364	likely benign	not provided		no assertion criteria provided	clinical testing