rs4804063

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3877A>G(p.Ser1293Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,611,874 control chromosomes in the GnomAD database, including 38,890 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4617 hom., cov: 28)

Exomes 𝑓: 0.21 ( 34273 hom. )

Consequence

FBN3
NM_032447.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.390

Publications

20 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=0.001069516).

BP6

Variant 19-8112061-T-C is Benign according to our data. Variant chr19-8112061-T-C is described in ClinVar as Benign. ClinVar VariationId is 1600962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.3877A>G	p.Ser1293Gly	missense_variant	Exon 31 of 64	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.3877A>G	p.Ser1293Gly	missense_variant	Exon 31 of 64	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.3877A>G	p.Ser1293Gly	missense_variant	Exon 30 of 63	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.3877A>G	p.Ser1293Gly	missense_variant	Exon 31 of 64	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.4003A>G	p.Ser1335Gly	missense_variant	Exon 31 of 64			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35633

AN:

151130

Hom.:

4602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.196

GnomAD2 exomes

AF:

0.253

AC:

63554

AN:

251100

AF XY:

0.251

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.207

AC:

302441

AN:

1460626

Hom.:

34273

Cov.:

AF XY:

0.210

AC XY:

152784

AN XY:

726656

show subpopulations

African (AFR)

AF:

0.278

AC:

9299

AN:

33448

American (AMR)

AF:

0.322

AC:

14369

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

4831

AN:

26102

East Asian (EAS)

AF:

0.307

AC:

12179

AN:

39660

South Asian (SAS)

AF:

0.361

AC:

31155

AN:

86200

European-Finnish (FIN)

AF:

0.278

AC:

14815

AN:

53344

Middle Eastern (MID)

AF:

0.165

AC:

953

AN:

5762

European-Non Finnish (NFE)

AF:

0.182

AC:

201880

AN:

1111100

Other (OTH)

AF:

0.215

AC:

12960

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

10446

20892

31338

41784

52230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7492

14984

22476

29968

37460

<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:

0.236

AC:

35663

AN:

151248

Hom.:

4617

Cov.:

AF XY:

0.245

AC XY:

18087

AN XY:

73870

show subpopulations

African (AFR)

AF:

0.276

AC:

11336

AN:

41114

American (AMR)

AF:

0.264

AC:

4006

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

660

AN:

3466

East Asian (EAS)

AF:

0.365

AC:

1863

AN:

5104

South Asian (SAS)

AF:

0.402

AC:

1914

AN:

4756

European-Finnish (FIN)

AF:

0.291

AC:

3055

AN:

10490

Middle Eastern (MID)

AF:

0.116

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.179

AC:

12119

AN:

67834

Other (OTH)

AF:

0.201

AC:

424

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1273

2547

3820

5094

6367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.190

Hom.:

14998

Bravo

AF:

0.231

TwinsUK

AF:

0.186

AC:

688

ALSPAC

AF:

0.186

AC:

715

ESP6500AA

AF:

0.272

AC:

1200

ESP6500EA

AF:

0.172

AC:

1480

ExAC

AF:

0.252

AC:

30587

Asia WGS

AF:

0.395

AC:

1370

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.64

.;.;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L

PhyloP100

-0.39

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.8

.;N;.

REVEL

Benign

0.12

Sift

Benign

0.37

.;T;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.080

MPC

0.17

ClinPred

0.0054

GERP RS

-5.6

Varity_R

0.036

gMVP

0.30

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over