15-48467094-G-T

Variant summary

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

The NM_000138.5(FBN1):​c.4747+844C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,986 control chromosomes in the GnomAD database, including 9,660 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 0.34 ( 9660 hom., cov: 32)

Consequence

FBN1
NM_000138.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.303
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=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBN1NM_000138.5 linkc.4747+844C>A intron_variant Intron 38 of 65 ENST00000316623.10 NP_000129.3 P35555
FBN1NM_001406716.1 linkc.4747+844C>A intron_variant Intron 37 of 64 NP_001393645.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBN1ENST00000316623.10 linkc.4747+844C>A intron_variant Intron 38 of 65 1 NM_000138.5 ENSP00000325527.5 P35555

Frequencies

GnomAD3 genomes
AF:
0.335
AC:
50854
AN:
151868
Hom.:
9624
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.523
Gnomad AMI
AF:
0.438
Gnomad AMR
AF:
0.296
Gnomad ASJ
AF:
0.199
Gnomad EAS
AF:
0.400
Gnomad SAS
AF:
0.244
Gnomad FIN
AF:
0.266
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.248
Gnomad OTH
AF:
0.313
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.335
AC:
50958
AN:
151986
Hom.:
9660
Cov.:
32
AF XY:
0.334
AC XY:
24840
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.524
Gnomad4 AMR
AF:
0.296
Gnomad4 ASJ
AF:
0.199
Gnomad4 EAS
AF:
0.402
Gnomad4 SAS
AF:
0.244
Gnomad4 FIN
AF:
0.266
Gnomad4 NFE
AF:
0.248
Gnomad4 OTH
AF:
0.312
Alfa
AF:
0.266
Hom.:
2728
Bravo
AF:
0.347
Asia WGS
AF:
0.346
AC:
1202
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.45
DANN
Benign
0.48

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: rs4774517; hg19: chr15-48759291; API