rs17160151

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032447.5(FBN3):c.6941G>A(p.Ser2314Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,594,920 control chromosomes in the GnomAD database, including 2,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 1227 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 1070 hom. )

Consequence

FBN3
NM_032447.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.977

Publications

7 publications found

Variant links:

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

FBN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036964118).

BP6

Variant 19-8085509-C-T is Benign according to our data. Variant chr19-8085509-C-T is described in ClinVar as Benign. ClinVar VariationId is 1601594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032447.5. 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
	FBN3	NM_032447.5	MANE Select	c.6941G>A	p.Ser2314Asn	missense	Exon 56 of 64	NP_115823.3
	FBN3	NM_001321431.2		c.6941G>A	p.Ser2314Asn	missense	Exon 56 of 64	NP_001308360.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FBN3	ENST00000600128.6	TSL:1 MANE Select	c.6941G>A	p.Ser2314Asn	missense	Exon 56 of 64	ENSP00000470498.1
FBN3	ENST00000270509.6	TSL:1	c.6941G>A	p.Ser2314Asn	missense	Exon 55 of 63	ENSP00000270509.2
FBN3	ENST00000601739.5	TSL:1	c.6941G>A	p.Ser2314Asn	missense	Exon 56 of 64	ENSP00000472324.1

Frequencies

GnomAD3 genomes

AF:

0.0683

AC:

10388

AN:

152128

Hom.:

1223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.0611

GnomAD2 exomes

AF:

0.0176

AC:

3779

AN:

215246

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000800

Gnomad OTH exome

AF:

0.00897

GnomAD4 exome

AF:

0.00753

AC:

10870

AN:

1442674

Hom.:

1070

Cov.:

AF XY:

0.00662

AC XY:

4739

AN XY:

715990

show subpopulations

African (AFR)

AF:

0.247

AC:

8175

AN:

33128

American (AMR)

AF:

0.0136

AC:

571

AN:

41990

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

460

AN:

25730

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38896

South Asian (SAS)

AF:

0.00226

AC:

188

AN:

83158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51126

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.000381

AC:

420

AN:

1103446

Other (OTH)

AF:

0.0167

AC:

993

AN:

59614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

487

973

1460

1946

2433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<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:

0.0684

AC:

10419

AN:

152246

Hom.:

1227

Cov.:

AF XY:

0.0666

AC XY:

4958

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.236

AC:

9799

AN:

41518

American (AMR)

AF:

0.0230

AC:

352

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

68016

Other (OTH)

AF:

0.0605

AC:

128

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

419

838

1257

1676

2095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0273

Hom.:

944

Bravo

AF:

0.0780

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.227

AC:

998

ESP6500EA

AF:

0.00222

AC:

ExAC

AF:

0.0203

AC:

2449

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FBN3-related disorder

Benign:1

Apr 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Benign

0.11

Eigen_PC

Benign

-0.036

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.5

PhyloP100

0.98

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Uncertain

0.018

Sift4G

Uncertain

0.029

Polyphen

1.0

Vest4

0.31

MPC

0.59

ClinPred

0.012

GERP RS

2.3

Varity_R

0.43

gMVP

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over