Variant rs3813774 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032447.5(FBN3):c.1929C>T(p.Cys643=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,614,004 control chromosomes in the GnomAD database, including 5,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1087 hom., cov: 33)

Exomes 𝑓: 0.068 ( 4536 hom. )

Consequence

FBN3
NM_032447.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.19

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 19-8131615-G-A is Benign according to our data. Variant chr19-8131615-G-A is described in ClinVar as [Benign]. Clinvar id is 1288401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 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.1929C>T	p.Cys643=	synonymous_variant	15/64	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FBN3	ENST00000600128.6 linkuse as main transcript	c.1929C>T	p.Cys643=	synonymous_variant	15/64	1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6 linkuse as main transcript	c.1929C>T	p.Cys643=	synonymous_variant	14/63	1		ENSP00000270509
FBN3	ENST00000601739.5 linkuse as main transcript	c.1929C>T	p.Cys643=	synonymous_variant	15/64	1		ENSP00000472324
FBN3	ENST00000651877.1 linkuse as main transcript	c.2055C>T	p.Cys685=	synonymous_variant	15/64			ENSP00000498507	P1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15311

AN:

152158

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0644

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0631

Gnomad OTH

AF:

0.0980

GnomAD3 exomes

AF:

0.0765

AC:

19208

AN:

251008

Hom.:

1168

AF XY:

0.0734

AC XY:

9960

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0459

Gnomad ASJ exome

AF:

0.0598

Gnomad EAS exome

AF:

0.222

Gnomad SAS exome

AF:

0.0578

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0609

Gnomad OTH exome

AF:

0.0699

GnomAD4 exome

AF:

0.0685

AC:

100073

AN:

1461728

Hom.:

4536

Cov.:

AF XY:

0.0678

AC XY:

49301

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.0487

Gnomad4 ASJ exome

AF:

0.0548

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.0600

Gnomad4 FIN exome

AF:

0.0294

Gnomad4 NFE exome

AF:

0.0613

Gnomad4 OTH exome

AF:

0.0742

GnomAD4 genome

AF:

0.101

AC:

15330

AN:

152276

Hom.:

1087

Cov.:

AF XY:

0.0987

AC XY:

7349

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.0643

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.0626

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.0631

Gnomad4 OTH

AF:

0.0970

Alfa

AF:

0.0730

Hom.:

969

Bravo

AF:

0.109

Asia WGS

AF:

0.105

AC:

368

AN:

3478

EpiCase

AF:

0.0654

EpiControl

AF:

0.0715

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2020	- -

FBN3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.9

DANN

Benign

0.51

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