rs11466030
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000243.3(MEFV):c.1587+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,612,596 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0082 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 13 hom. )
Consequence
MEFV
NM_000243.3 intron
NM_000243.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.68
Genes affected
MEFV (HGNC:6998): (MEFV innate immunity regulator, pyrin) This gene encodes a protein, also known as pyrin or marenostrin, that is an important modulator of innate immunity. Mutations in this gene are associated with Mediterranean fever, a hereditary periodic fever syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 16-3246998-G-A is Benign according to our data. Variant chr16-3246998-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3246998-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00825 (1256/152292) while in subpopulation AFR AF= 0.0271 (1128/41560). AF 95% confidence interval is 0.0258. There are 20 homozygotes in gnomad4. There are 602 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEFV | NM_000243.3 | c.1587+18C>T | intron_variant | ENST00000219596.6 | |||
MEFV | NM_001198536.2 | c.954+18C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEFV | ENST00000219596.6 | c.1587+18C>T | intron_variant | 1 | NM_000243.3 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00823 AC: 1253AN: 152174Hom.: 20 Cov.: 32
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GnomAD3 exomes AF: 0.00248 AC: 621AN: 250266Hom.: 10 AF XY: 0.00176 AC XY: 239AN XY: 135422
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GnomAD4 exome AF: 0.000807 AC: 1178AN: 1460304Hom.: 13 Cov.: 30 AF XY: 0.000709 AC XY: 515AN XY: 726520
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GnomAD4 genome AF: 0.00825 AC: 1256AN: 152292Hom.: 20 Cov.: 32 AF XY: 0.00808 AC XY: 602AN XY: 74460
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 14, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 21, 2016 | Variant summary: The MEFV c.1587+18C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 375/120722 control chromosomes (5 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0311653 (322/10332). This frequency is slightly above the estimated maximal expected allele frequency of a pathogenic MEFV variant (0.0216506), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Based on high frequency in controls and in silico splicing predictions, this variant was classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 28, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | MEFV: BS1, BS2 - |
Familial Mediterranean fever Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 18, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Acute febrile neutrophilic dermatosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Familial Mediterranean fever, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at