rs16960979

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000138.5(FBN1):​c.4336+399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 152,366 control chromosomes in the GnomAD database, including 238 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 0.017 ( 238 hom., cov: 32)

Consequence

FBN1
NM_000138.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.779
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 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 = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBN1NM_000138.5 linkuse as main transcriptc.4336+399A>G intron_variant ENST00000316623.10 NP_000129.3 P35555
FBN1NM_001406716.1 linkuse as main transcriptc.4336+399A>G intron_variant NP_001393645.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBN1ENST00000316623.10 linkuse as main transcriptc.4336+399A>G intron_variant 1 NM_000138.5 ENSP00000325527.5 P35555

Frequencies

GnomAD3 genomes
AF:
0.0171
AC:
2600
AN:
152248
Hom.:
234
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00463
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0477
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.263
Gnomad SAS
AF:
0.0352
Gnomad FIN
AF:
0.00329
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000999
Gnomad OTH
AF:
0.0201
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0171
AC:
2611
AN:
152366
Hom.:
238
Cov.:
32
AF XY:
0.0202
AC XY:
1505
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.00466
Gnomad4 AMR
AF:
0.0481
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.264
Gnomad4 SAS
AF:
0.0352
Gnomad4 FIN
AF:
0.00329
Gnomad4 NFE
AF:
0.000999
Gnomad4 OTH
AF:
0.0199
Alfa
AF:
0.0124
Hom.:
13
Bravo
AF:
0.0209
Asia WGS
AF:
0.139
AC:
482
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
10
DANN
Benign
0.77

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: rs16960979; hg19: chr15-48764349; API