Variant 19-8096013-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000600128.6(FBN3):c.5607C>G(p.Asn1869Lys) variant causes a missense change. The variant allele was found at a frequency of 0.133 in 1,613,168 control chromosomes in the GnomAD database, including 16,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1397 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14616 hom. )

Consequence

FBN3
ENST00000600128.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.12

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037261546).

BP6

Variant 19-8096013-G-C is Benign according to our data. Variant chr19-8096013-G-C is described in ClinVar as [Benign]. Clinvar id is 1537877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8096013-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5 linkuse as main transcript	c.5607C>G	p.Asn1869Lys	missense_variant	45/64	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6 linkuse as main transcript	c.5607C>G	p.Asn1869Lys	missense_variant	45/64	1	NM_032447.5	ENSP00000470498

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

18018

AN:

152074

Hom.:

1393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.0956

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.150

AC:

37721

AN:

251302

Hom.:

3428

AF XY:

0.147

AC XY:

19999

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.135

AC:

197306

AN:

1460974

Hom.:

14616

Cov.:

AF XY:

0.135

AC XY:

97970

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.0258

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.0915

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.118

AC:

18031

AN:

152194

Hom.:

1397

Cov.:

AF XY:

0.122

AC XY:

9053

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.0956

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.118

Hom.:

955

Bravo

AF:

0.118

TwinsUK

AF:

0.143

AC:

529

ALSPAC

AF:

0.128

AC:

495

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.133

AC:

1141

ExAC

AF:

0.140

AC:

17006

Asia WGS

AF:

0.156

AC:

539

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

.;.;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;N;N

MutationTaster

Benign

6.2e-8

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.4

.;D;.

REVEL

Uncertain

0.36

Sift

Benign

0.31

.;T;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.33

B;B;B

Vest4

0.24

MutPred

0.34

Gain of methylation at N1869 (P = 0.0022);Gain of methylation at N1869 (P = 0.0022);Gain of methylation at N1869 (P = 0.0022);

MPC

0.57

ClinPred

0.057

GERP RS

3.7

Varity_R

0.41

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over