chr15-48504949-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000138.5(FBN1):​c.1960+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,576,856 control chromosomes in the GnomAD database, including 2,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 278 hom., cov: 33)
Exomes 𝑓: 0.058 ( 2688 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0450
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 15-48504949-C-T is Benign according to our data. Variant chr15-48504949-C-T is described in ClinVar as [Benign]. Clinvar id is 674484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBN1NM_000138.5 linkuse as main transcriptc.1960+76G>A intron_variant ENST00000316623.10 NP_000129.3 P35555
FBN1NM_001406716.1 linkuse as main transcriptc.1960+76G>A intron_variant NP_001393645.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBN1ENST00000316623.10 linkuse as main transcriptc.1960+76G>A intron_variant 1 NM_000138.5 ENSP00000325527.5 P35555

Frequencies

GnomAD3 genomes
AF:
0.0499
AC:
7595
AN:
152096
Hom.:
277
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0133
Gnomad AMI
AF:
0.0670
Gnomad AMR
AF:
0.0648
Gnomad ASJ
AF:
0.0576
Gnomad EAS
AF:
0.153
Gnomad SAS
AF:
0.0900
Gnomad FIN
AF:
0.0742
Gnomad MID
AF:
0.0414
Gnomad NFE
AF:
0.0535
Gnomad OTH
AF:
0.0607
GnomAD4 exome
AF:
0.0578
AC:
82298
AN:
1424642
Hom.:
2688
AF XY:
0.0584
AC XY:
41521
AN XY:
711284
show subpopulations
Gnomad4 AFR exome
AF:
0.0102
Gnomad4 AMR exome
AF:
0.0823
Gnomad4 ASJ exome
AF:
0.0589
Gnomad4 EAS exome
AF:
0.139
Gnomad4 SAS exome
AF:
0.0837
Gnomad4 FIN exome
AF:
0.0796
Gnomad4 NFE exome
AF:
0.0518
Gnomad4 OTH exome
AF:
0.0643
GnomAD4 genome
AF:
0.0499
AC:
7596
AN:
152214
Hom.:
278
Cov.:
33
AF XY:
0.0512
AC XY:
3812
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0132
Gnomad4 AMR
AF:
0.0648
Gnomad4 ASJ
AF:
0.0576
Gnomad4 EAS
AF:
0.152
Gnomad4 SAS
AF:
0.0885
Gnomad4 FIN
AF:
0.0742
Gnomad4 NFE
AF:
0.0535
Gnomad4 OTH
AF:
0.0662
Alfa
AF:
0.0536
Hom.:
241
Bravo
AF:
0.0473
Asia WGS
AF:
0.164
AC:
570
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.5
DANN
Benign
0.31

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: rs17361868; hg19: chr15-48797146; API