Submissions for variant NM_000243.3(MEFV):c.*9C>T

gnomAD frequency: 0.00618  dbSNP: rs11466048

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514937	SCV000610008	likely benign	not provided	2017-03-09	criteria provided, single submitter	clinical testing
Invitae	RCV001079215	SCV000629015	benign	Familial Mediterranean fever	2023-08-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000722126	SCV000696038	benign	not specified	2021-05-22	criteria provided, single submitter	clinical testing	Variant summary: MEFV c.*9C>T alters a non-conserved nucleotide located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.002 in 251240 control chromosomes, predominantly at a frequency of 0.025 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.15 fold of the estimated maximal expected allele frequency for a pathogenic variant in MEFV causing Familial Mediterranean Fever phenotype (0.022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.*9C>T has been reported in the literature with a non-informative genotype in at-least one one individual affected with PFAPA (Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome) syndrome ( example, Kolly_2012). This report does not provide unequivocal conclusions about association of the variant with Familial Mediterranean Fever. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=1, likely benign, n=2, benign, n=1). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000514937	SCV000885683	likely benign	not provided	2021-10-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001079215	SCV001277617	uncertain significance	Familial Mediterranean fever	2017-04-28	criteria provided, single submitter	clinical testing	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.
GeneDx	RCV000514937	SCV001883750	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263721	SCV002543379	likely benign	Autoinflammatory syndrome	2021-06-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514937	SCV002563298	benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	MEFV: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV004535656	SCV004739435	benign	MEFV-related disorder	2019-03-04	criteria provided, single submitter	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).
Natera, Inc.	RCV001079215	SCV002093866	benign	Familial Mediterranean fever	2019-10-18	no assertion criteria provided	clinical testing