rs200841830

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000138.5(FBN1):​c.6314-15G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,342 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FBN1
NM_000138.5 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.855
Variant links:
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FBN1NM_000138.5 linkuse as main transcriptc.6314-15G>T splice_polypyrimidine_tract_variant, intron_variant ENST00000316623.10
FBN1NM_001406716.1 linkuse as main transcriptc.6314-15G>T splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FBN1ENST00000316623.10 linkuse as main transcriptc.6314-15G>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_000138.5 P1
FBN1ENST00000559133.6 linkuse as main transcriptc.6314-15G>T splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant 1
FBN1ENST00000537463.6 linkuse as main transcriptc.*2077-15G>T splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant 5
FBN1ENST00000674301.2 linkuse as main transcriptc.6314-15G>T splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250062
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135176
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449342
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
721798
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
2.6
DANN
Benign
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200841830; hg19: chr15-48729599; API