15-48534224-CAGAG-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_000138.5(FBN1):c.737-23_737-20del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,429,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000091 ( 0 hom. )
Consequence
FBN1
NM_000138.5 intron
NM_000138.5 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.18
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 Likely_benign. Variant got -6 ACMG points.
BP6
Variant 15-48534224-CAGAG-C is Benign according to our data. Variant chr15-48534224-CAGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 2924670.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.737-23_737-20del | intron_variant | ENST00000316623.10 | |||
FBN1 | NM_001406716.1 | c.737-23_737-20del | intron_variant | ||||
FBN1 | NM_001406717.1 | c.737-23_737-20del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.737-23_737-20del | intron_variant | 1 | NM_000138.5 | P1 | |||
FBN1 | ENST00000559133.6 | c.737-23_737-20del | intron_variant, NMD_transcript_variant | 1 | |||||
FBN1 | ENST00000537463.6 | c.636+3483_636+3486del | intron_variant, NMD_transcript_variant | 5 | |||||
FBN1 | ENST00000674301.2 | c.737-23_737-20del | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000909 AC: 13AN: 1429706Hom.: 0 AF XY: 0.00000281 AC XY: 2AN XY: 710974
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
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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