rs187254268
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000138.5(FBN1):āc.405A>Gā(p.Leu135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,956 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 (ā ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000078 ( 0 hom. )
Consequence
FBN1
NM_000138.5 synonymous
NM_000138.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.943
Genes affected
FBN1 (HGNC:3603): (fibrillin 1) This gene encodes a member of the fibrillin family of proteins. The encoded preproprotein is proteolytically processed to generate two proteins including the extracellular matrix component fibrillin-1 and the protein hormone asprosin. Fibrillin-1 is an extracellular matrix glycoprotein that serves as a structural component of calcium-binding microfibrils. These microfibrils provide force-bearing structural support in elastic and nonelastic connective tissue throughout the body. Asprosin, secreted by white adipose tissue, has been shown to regulate glucose homeostasis. Mutations in this gene are associated with Marfan syndrome and the related MASS phenotype, as well as ectopia lentis syndrome, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome and neonatal progeroid syndrome. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 15-48600176-T-C is Benign according to our data. Variant chr15-48600176-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 527230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.943 with no splicing effect.
BS2
?
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.405A>G | p.Leu135= | synonymous_variant | 5/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.405A>G | p.Leu135= | synonymous_variant | 4/65 | ||
FBN1 | NM_001406717.1 | c.405A>G | p.Leu135= | synonymous_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.405A>G | p.Leu135= | synonymous_variant | 5/66 | 1 | NM_000138.5 | P1 | |
FBN1 | ENST00000559133.6 | c.405A>G | p.Leu135= | synonymous_variant, NMD_transcript_variant | 5/67 | 1 | |||
FBN1 | ENST00000674301.2 | c.405A>G | p.Leu135= | synonymous_variant, NMD_transcript_variant | 5/68 | ||||
FBN1 | ENST00000537463.6 | c.405A>G | p.Leu135= | synonymous_variant, NMD_transcript_variant | 5/31 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251174Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135738
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GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461652Hom.: 0 Cov.: 30 AF XY: 0.0000605 AC XY: 44AN XY: 727142
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2019 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 16, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 31, 2020 | - - |
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 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