ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.1260+10C>T (rs104895137)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000030170 SCV000753985 benign Familial Mediterranean fever 2020-11-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000668 SCV001157698 likely benign not specified 2019-05-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000030170 SCV001277729 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001280974 SCV001468355 uncertain significance Familial Mediterranean fever; Familial mediterranean fever, autosomal dominant 2020-09-30 criteria provided, single submitter clinical testing MEFV NM_000243.2 exon 3 c.1260+10C>T: This variant has not been reported in the literature but is present in 0.9% (96/10270) of Ashkenazi Jewish alleles, including 1 homozygote, in the Genome Aggregation Database ( This variant is present in ClinVar (Variation ID:36498) and is also present in the InFevers database ( Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001000668 SCV000052830 likely benign not specified 2020-06-05 no assertion criteria provided clinical testing MEFV c.1260+10C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00057 in 247282 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.00057 vs 0.022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1260+10C>T in individuals affected with Familial Mediterranean Fever and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign (n=2) and as uncertain significance (n=1). In 2018, the expert's international study group for systemic autoinflammatory diseases (INSAID) reported a 'validated' classification of 'likely benign'for the variant (Van Gijn_2018). Based on the evidence outlined above, the variant was classified as likely benign.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000030170 SCV000115774 not provided Familial Mediterranean fever no assertion provided not provided

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