Submissions for variant NM_000243.3(MEFV):c.1610+8G>A

gnomAD frequency: 0.00006  dbSNP: rs765410591

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001810995	SCV000604194	likely benign	not provided	2023-11-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001429606	SCV001632323	likely benign	Familial Mediterranean fever	2024-12-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496968	SCV002806581	likely benign	Familial Mediterranean fever; Familial Mediterranean fever, autosomal dominant; Acute febrile neutrophilic dermatosis	2021-08-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001429606	SCV003802080	uncertain significance	Familial Mediterranean fever	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126778	SCV003802081	likely benign	Familial Mediterranean fever, autosomal dominant	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126779	SCV003802082	benign	Acute febrile neutrophilic dermatosis	2023-02-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005056099	SCV005726796	uncertain significance	not specified	2024-11-11	criteria provided, single submitter	clinical testing	Variant summary: MEFV c.1610+8G>A 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. Consensus agreement among computation 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 0.0002 in 251392 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.0002 vs 0.022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1610+8G>A in individuals affected with Familial Mediterranean Fever and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 439886). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004541587	SCV004760800	likely benign	MEFV-related disorder	2019-12-24	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).