15-48487034-GTAAAATAAAATAAAA-GTAAAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000138.5(FBN1):c.3589+31_3589+40delTTTTATTTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000437 in 1,280,746 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.919

Publications

3 publications found

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]

FBN1 Gene-Disease associations (from GenCC):

familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Marfan syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P, PanelApp Australia, Orphanet, Ambry Genetics
Acromicric dysplasia
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
progeroid and marfanoid aspect-lipodystrophy syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
stiff skin syndrome
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Weill-Marchesani syndrome 2, dominant
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
geleophysic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated ectopia lentis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
neonatal Marfan syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Weill-Marchesani syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ectopia lentis 1, isolated, autosomal dominant
Inheritance: AD Classification: LIMITED Submitted by: G2P
Shprintzen-Goldberg syndrome
Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

FBN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000138.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN1	NM_000138.5	MANE Select	c.3589+31_3589+40delTTTTATTTTA		intron	N/A	NP_000129.3
	FBN1	NM_001406716.1		c.3589+31_3589+40delTTTTATTTTA		intron	N/A	NP_001393645.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBN1	ENST00000316623.10	TSL:1 MANE Select	c.3589+31_3589+40delTTTTATTTTA	intron	N/A	ENSP00000325527.5
FBN1	ENST00000559133.6	TSL:1	n.3589+31_3589+40delTTTTATTTTA	intron	N/A	ENSP00000453958.2
FBN1	ENST00000537463.6	TSL:5	n.637-12394_637-12385delTTTTATTTTA	intron	N/A	ENSP00000440294.2

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150370

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000736

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000819

AC:

AN:

85474

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.000575

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000844

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000442

AC:

AN:

1130260

Hom.:

AF XY:

0.0000501

AC XY:

AN XY:

559178

show subpopulations

African (AFR)

AF:

0.0000884

AC:

AN:

22624

American (AMR)

AF:

0.00

AC:

AN:

17906

Ashkenazi Jewish (ASJ)

AF:

0.0000506

AC:

AN:

19746

East Asian (EAS)

AF:

0.000156

AC:

AN:

32060

South Asian (SAS)

AF:

0.0000205

AC:

AN:

48720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39942

Middle Eastern (MID)

AF:

0.000304

AC:

AN:

3292

European-Non Finnish (NFE)

AF:

0.0000411

AC:

AN:

899238

Other (OTH)

AF:

0.0000642

AC:

AN:

46732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000399

AC:

AN:

150486

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73466

show subpopulations

African (AFR)

AF:

0.0000734

AC:

AN:

40894

American (AMR)

AF:

0.000132

AC:

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67632

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.92

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over