rs16961232
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000138.5(FBN1):c.347-3260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 152,374 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.015 ( 205 hom., cov: 32)
Consequence
FBN1
NM_000138.5 intron
NM_000138.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0690
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.347-3260T>C | intron_variant | ENST00000316623.10 | |||
FBN1 | NM_001406716.1 | c.347-3260T>C | intron_variant | ||||
FBN1 | NM_001406717.1 | c.347-3260T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.347-3260T>C | intron_variant | 1 | NM_000138.5 | P1 | |||
FBN1 | ENST00000559133.6 | c.347-3260T>C | intron_variant, NMD_transcript_variant | 1 | |||||
FBN1 | ENST00000537463.6 | c.347-3260T>C | intron_variant, NMD_transcript_variant | 5 | |||||
FBN1 | ENST00000674301.2 | c.347-3260T>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0152 AC: 2311AN: 152256Hom.: 203 Cov.: 32
GnomAD3 genomes
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0152 AC: 2320AN: 152374Hom.: 205 Cov.: 32 AF XY: 0.0178 AC XY: 1327AN XY: 74514
GnomAD4 genome
?
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32
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1327
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74514
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410
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
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