chr16-3243132-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000243.3(MEFV):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,612,458 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000243.3 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00666 AC: 1013AN: 152184Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00203 AC: 511AN: 251240Hom.: 2 AF XY: 0.00154 AC XY: 209AN XY: 135832
GnomAD4 exome AF: 0.000753 AC: 1100AN: 1460156Hom.: 9 Cov.: 31 AF XY: 0.000677 AC XY: 492AN XY: 726410
GnomAD4 genome AF: 0.00667 AC: 1016AN: 152302Hom.: 7 Cov.: 32 AF XY: 0.00651 AC XY: 485AN XY: 74470
ClinVar
Submissions by phenotype
not provided Benign:4
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MEFV: BS1, BS2 -
Familial Mediterranean fever Uncertain:1Benign:2
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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. -
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not specified Benign:1
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. -
Autoinflammatory syndrome Benign:1
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MEFV-related disorder Benign:1
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). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at