15-48487034-GTAAAA-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000138.5(FBN1):c.3589+36_3589+40del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,279,136 control chromosomes in the GnomAD database, including 17,597 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2094 hom., cov: 29)
Exomes 𝑓: 0.15 ( 15503 hom. )
Consequence
FBN1
NM_000138.5 intron
NM_000138.5 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
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 -16 ACMG points.
BP6
Variant 15-48487034-GTAAAA-G is Benign according to our data. Variant chr15-48487034-GTAAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 255294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48487034-GTAAAA-G is described in Lovd as [Benign]. Variant chr15-48487034-GTAAAA-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.3589+36_3589+40del | intron_variant | ENST00000316623.10 | NP_000129.3 | |||
FBN1 | NM_001406716.1 | c.3589+36_3589+40del | intron_variant | NP_001393645.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.3589+36_3589+40del | intron_variant | 1 | NM_000138.5 | ENSP00000325527 | P1 |
Frequencies
GnomAD3 genomes AF: 0.164 AC: 24574AN: 150246Hom.: 2086 Cov.: 29
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GnomAD3 exomes AF: 0.175 AC: 14975AN: 85474Hom.: 1542 AF XY: 0.169 AC XY: 8044AN XY: 47730
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GnomAD4 exome AF: 0.153 AC: 172360AN: 1128774Hom.: 15503 AF XY: 0.153 AC XY: 85461AN XY: 558522
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GnomAD4 genome AF: 0.164 AC: 24615AN: 150362Hom.: 2094 Cov.: 29 AF XY: 0.167 AC XY: 12295AN XY: 73410
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, flagged submission | clinical testing | GeneDx | Jun 14, 2013 | The variant is found in TAAD panel(s). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at