16-3247148-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000243.3(MEFV):c.1455G>A(p.Glu485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
MEFV
NM_000243.3 synonymous
NM_000243.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.602
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
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Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 16-3247148-C-T is Benign according to our data. Variant chr16-3247148-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 565686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=-0.602 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEFV | NM_000243.3 | c.1455G>A | p.Glu485= | synonymous_variant | 5/10 | ENST00000219596.6 | |
MEFV | NM_001198536.2 | c.822G>A | p.Glu274= | synonymous_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEFV | ENST00000219596.6 | c.1455G>A | p.Glu485= | synonymous_variant | 5/10 | 1 | NM_000243.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461882Hom.: 0 Cov.: 65 AF XY: 0.00000275 AC XY: 2AN XY: 727244
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial Mediterranean fever Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 02, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at