rs13598

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000138.5(FBN1):c.*730G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,624 control chromosomes in the GnomAD database, including 61,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61361 hom., cov: 31)

Exomes 𝑓: 0.79 ( 143 hom. )

Consequence

FBN1
NM_000138.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.96

Publications

9 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):

Marfan syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Genomics England PanelApp
familial thoracic aortic aneurysm and aortic dissection
Inheritance: Unknown, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Acromicric dysplasia
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
progeroid and marfanoid aspect-lipodystrophy syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
stiff skin syndrome
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

FBN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-48410260-C-A is Benign according to our data. Variant chr15-48410260-C-A is described in ClinVar as Benign. ClinVar VariationId is 316351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN1	NM_000138.5	MANE Select	c.*730G>T		3_prime_UTR	Exon 66 of 66	NP_000129.3
	FBN1	NM_001406716.1		c.*730G>T		3_prime_UTR	Exon 65 of 65	NP_001393645.1	P35555

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBN1	ENST00000316623.10	TSL:1 MANE Select	c.*730G>T	3_prime_UTR	Exon 66 of 66	ENSP00000325527.5	P35555
FBN1	ENST00000559133.6	TSL:1	n.*2154G>T	non_coding_transcript_exon	Exon 67 of 67	ENSP00000453958.2	H0YND0
FBN1	ENST00000559133.6	TSL:1	n.*2154G>T	3_prime_UTR	Exon 67 of 67	ENSP00000453958.2	H0YND0

Frequencies

GnomAD3 genomes

AF:

0.897

AC:

136440

AN:

152050

Hom.:

61309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.940

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.913

Gnomad ASJ

AF:

0.962

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.920

Gnomad FIN

AF:

0.815

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.874

Gnomad OTH

AF:

0.902

GnomAD4 exome

AF:

0.794

AC:

362

AN:

456

Hom.:

143

Cov.:

AF XY:

0.788

AC XY:

216

AN XY:

274

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.791

AC:

337

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.897

AC:

136550

AN:

152168

Hom.:

61361

Cov.:

AF XY:

0.896

AC XY:

66641

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.940

AC:

39022

AN:

41526

American (AMR)

AF:

0.913

AC:

13959

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.962

AC:

3341

AN:

3472

East Asian (EAS)

AF:

0.926

AC:

4800

AN:

5182

South Asian (SAS)

AF:

0.920

AC:

4429

AN:

4816

European-Finnish (FIN)

AF:

0.815

AC:

8616

AN:

10568

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.874

AC:

59467

AN:

68004

Other (OTH)

AF:

0.903

AC:

1908

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

723

1446

2168

2891

3614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.891

Hom.:

60476

Bravo

AF:

0.906

Asia WGS

AF:

0.939

AC:

3267

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Acromicric dysplasia (1)

Ectopia lentis 1, isolated, autosomal dominant (1)

Familial thoracic aortic aneurysm and aortic dissection (1)

Geleophysic dysplasia (1)

Marfan syndrome (1)

Stiff skin syndrome (1)

Weill-Marchesani syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.1

(source)

DANN

Benign

0.89

PhyloP100

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over