Variant chr19-8087841-A-G 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.6603T>C(p.Asp2201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,613,476 control chromosomes in the GnomAD database, including 411,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43759 hom., cov: 31)

Exomes 𝑓: 0.71 ( 367647 hom. )

Consequence

FBN3
NM_032447.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.492

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=-0.66).

BP6

Variant 19-8087841-A-G is Benign according to our data. Variant chr19-8087841-A-G is described in ClinVar as [Benign]. Clinvar id is 1603105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8087841-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.492 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 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.6603T>C	p.Asp2201=	synonymous_variant	53/64	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.6603T>C	p.Asp2201=	synonymous_variant	53/64	1	NM_032447.5	ENSP00000470498

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114034

AN:

151884

Hom.:

43698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.902

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.733

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.765

GnomAD3 exomes

AF:

0.681

AC:

171020

AN:

251266

Hom.:

59494

AF XY:

0.677

AC XY:

91985

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.906

Gnomad AMR exome

AF:

0.644

Gnomad ASJ exome

AF:

0.724

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.706

AC:

1031566

AN:

1461474

Hom.:

367647

Cov.:

AF XY:

0.702

AC XY:

510257

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.908

Gnomad4 AMR exome

AF:

0.655

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.569

Gnomad4 FIN exome

AF:

0.654

Gnomad4 NFE exome

AF:

0.722

Gnomad4 OTH exome

AF:

0.711

GnomAD4 genome

AF:

0.751

AC:

114143

AN:

152002

Hom.:

43759

Cov.:

AF XY:

0.741

AC XY:

55050

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.902

Gnomad4 AMR

AF:

0.709

Gnomad4 ASJ

AF:

0.733

Gnomad4 EAS

AF:

0.494

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.722

Gnomad4 OTH

AF:

0.758

Alfa

AF:

0.750

Hom.:

19127

Bravo

AF:

0.769

Asia WGS

AF:

0.530

AC:

1844

AN:

3478

EpiCase

AF:

0.726

EpiControl

AF:

0.728

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.089

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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