Submissions for variant NM_000243.3(MEFV):c.1467G>A (p.Gln489=)

gnomAD frequency: 0.00341  dbSNP: rs61732424

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000126746	SCV000170258	benign	not specified	2011-10-24	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590572	SCV000604169	benign	not provided	2023-04-14	criteria provided, single submitter	clinical testing
Invitae	RCV000083698	SCV000629023	benign	Familial Mediterranean fever	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590572	SCV000696049	likely benign	not provided	2017-02-01	criteria provided, single submitter	clinical testing	Variant summary: The MEFV c.1467G>A (p.Gln489Gln) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this substitution along with 5/5 splice prediction tools predicting the variant not to have a significance impact on normal splicing. The variant was found in 460/121412 control chromosomes (2 homozygotes) at a frequency of 0.0037888, which does not exceed the estimated maximal expected allele frequency of a pathogenic MEFV variant (0.0216506). The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. In addition, a clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000590572	SCV001150751	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	MEFV: BP4, BP7, BS2
Illumina Laboratory Services, Illumina	RCV000083698	SCV001276007	uncertain significance	Familial Mediterranean fever	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262632	SCV002543708	benign	Autoinflammatory syndrome	2022-02-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002390250	SCV002697482	likely benign	Inborn genetic diseases	2022-02-17	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.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000083698	SCV000115787	not provided	Familial Mediterranean fever		no assertion provided	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000126746	SCV001740473	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000590572	SCV001929533	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000083698	SCV002087403	likely benign	Familial Mediterranean fever	2019-12-19	no assertion criteria provided	clinical testing