rs3829817

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_032447.5(FBN3):c.5417G>A(p.Arg1806Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,610,228 control chromosomes in the GnomAD database, including 39,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1806W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.20 ( 3072 hom., cov: 31)

Exomes 𝑓: 0.22 ( 36506 hom. )

Consequence

FBN3
NM_032447.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.25

Publications

24 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 -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 19-8096566-C-T is Benign according to our data. Variant chr19-8096566-C-T is described in ClinVar as Benign. ClinVar VariationId is 1567977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.5417G>A	p.Arg1806Gln	missense	Exon 44 of 64	NP_115823.3
	FBN3	NM_001321431.2		c.5417G>A	p.Arg1806Gln	missense	Exon 44 of 64	NP_001308360.1	Q75N90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBN3	ENST00000600128.6	TSL:1 MANE Select	c.5417G>A	p.Arg1806Gln	missense	Exon 44 of 64	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6	TSL:1	c.5417G>A	p.Arg1806Gln	missense	Exon 43 of 63	ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5	TSL:1	c.5417G>A	p.Arg1806Gln	missense	Exon 44 of 64	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29805

AN:

151938

Hom.:

3065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.212

AC:

52636

AN:

248090

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.222

AC:

323939

AN:

1458170

Hom.:

36506

Cov.:

AF XY:

0.223

AC XY:

161428

AN XY:

725164

show subpopulations

African (AFR)

AF:

0.139

AC:

4643

AN:

33450

American (AMR)

AF:

0.192

AC:

8565

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

7041

AN:

25964

East Asian (EAS)

AF:

0.201

AC:

7992

AN:

39666

South Asian (SAS)

AF:

0.229

AC:

19699

AN:

85932

European-Finnish (FIN)

AF:

0.202

AC:

10512

AN:

52024

Middle Eastern (MID)

AF:

0.243

AC:

1382

AN:

5690

European-Non Finnish (NFE)

AF:

0.226

AC:

250725

AN:

1110610

Other (OTH)

AF:

0.222

AC:

13380

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

13025

26050

39074

52099

65124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8638

17276

25914

34552

43190

<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:

0.196

AC:

29838

AN:

152058

Hom.:

3072

Cov.:

AF XY:

0.195

AC XY:

14502

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.143

AC:

5914

AN:

41484

American (AMR)

AF:

0.200

AC:

3050

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

876

AN:

3468

East Asian (EAS)

AF:

0.168

AC:

869

AN:

5160

South Asian (SAS)

AF:

0.219

AC:

1052

AN:

4812

European-Finnish (FIN)

AF:

0.195

AC:

2061

AN:

10594

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15300

AN:

67950

Other (OTH)

AF:

0.210

AC:

443

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1217

2434

3650

4867

6084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.217

Hom.:

9093

Bravo

AF:

0.195

TwinsUK

AF:

0.221

AC:

820

ALSPAC

AF:

0.221

AC:

851

ESP6500AA

AF:

0.153

AC:

673

ESP6500EA

AF:

0.227

AC:

1952

ExAC

AF:

0.212

AC:

25716

Asia WGS

AF:

0.206

AC:

719

AN:

3478

EpiCase

AF:

0.235

EpiControl

AF:

0.236

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

FBN3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.17

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

2.3

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.19

Sift

Benign

0.21

Sift4G

Benign

0.30

Polyphen

0.017

Vest4

0.072

MPC

0.28

ClinPred

0.019

GERP RS

-1.5

Varity_R

0.064

gMVP

0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.62

Position offset: -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

Computational scores

Splicing

Publications

Other links and lift over