Variant chr19-8131624-G-C 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.1920C>G(p.Ser640=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,613,934 control chromosomes in the GnomAD database, including 101,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7007 hom., cov: 33)

Exomes 𝑓: 0.35 ( 94138 hom. )

Consequence

FBN3
NM_032447.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.09

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 19-8131624-G-C is Benign according to our data. Variant chr19-8131624-G-C is described in ClinVar as [Benign]. Clinvar id is 1600060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8131624-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 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.1920C>G	p.Ser640=	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.1920C>G	p.Ser640=	synonymous_variant	15/64	1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6 linkuse as main transcript	c.1920C>G	p.Ser640=	synonymous_variant	14/63	1		ENSP00000270509
FBN3	ENST00000601739.5 linkuse as main transcript	c.1920C>G	p.Ser640=	synonymous_variant	15/64	1		ENSP00000472324
FBN3	ENST00000651877.1 linkuse as main transcript	c.2046C>G	p.Ser682=	synonymous_variant	15/64			ENSP00000498507	P1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42710

AN:

152100

Hom.:

7008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.291

AC:

73104

AN:

250978

Hom.:

12417

AF XY:

0.299

AC XY:

40580

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.0506

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.349

AC:

509848

AN:

1461716

Hom.:

94138

Cov.:

AF XY:

0.347

AC XY:

252525

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.389

Gnomad4 EAS exome

AF:

0.0518

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.281

AC:

42704

AN:

152218

Hom.:

7007

Cov.:

AF XY:

0.274

AC XY:

20399

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.0517

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.327

Hom.:

2818

Bravo

AF:

0.271

Asia WGS

AF:

0.145

AC:

503

AN:

3478

EpiCase

AF:

0.397

EpiControl

AF:

0.391

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	- -

FBN3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.73

CADD

Benign

0.027

DANN

Benign

0.37

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