Submissions for variant NM_003640.5(ELP1):c.3876T>G (p.Thr1292=)

gnomAD frequency: 0.01463  dbSNP: rs61749202

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000297833	SCV000476540	uncertain significance	Familial dysautonomia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000590763	SCV000563260	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590763	SCV000698213	benign	not provided	2017-08-22	criteria provided, single submitter	clinical testing	Variant summary: The c.3876T>G (p.Thr1292=) in IKBKAP gene is a synonymous change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control dataset of ExAC at a frequency of 0.01362 (1653/121382 chrs tested, including 21 homozygotes), predominantly in individuals of European Ancestry descent (0.01845; 1231/66722 chrs tested, including 17 homozygotes). These frequencies exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.0018). The variant of interest has not, to our knowledge, been reported in affected individuals via published reports, but is cited as Benign by a reputable clinical laboratory. Taken together, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590763	SCV001159187	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000297833	SCV001712301	benign	Familial dysautonomia	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000590763	SCV001759533	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000297833	SCV002081999	likely benign	Familial dysautonomia	2017-05-10	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003970072	SCV004793582	benign	ELP1-related disorder	2019-07-24	no assertion criteria provided	clinical testing	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).