Variant chr19-8094525-G-T 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.5826C>A(p.Pro1942Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,612,836 control chromosomes in the GnomAD database, including 340,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 29223 hom., cov: 33)

Exomes 𝑓: 0.65 ( 311388 hom. )

Consequence

FBN3
NM_032447.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.12

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:

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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=-0.56).

BP6

Variant 19-8094525-G-T is Benign according to our data. Variant chr19-8094525-G-T is described in ClinVar as [Benign]. Clinvar id is 1277303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8094525-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 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.5826C>A	p.Pro1942Pro	synonymous_variant	47/64	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 linkuse as main transcript	c.5826C>A	p.Pro1942Pro	synonymous_variant	47/64	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 linkuse as main transcript	c.5826C>A	p.Pro1942Pro	synonymous_variant	46/63	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 linkuse as main transcript	c.5826C>A	p.Pro1942Pro	synonymous_variant	47/64	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 linkuse as main transcript	c.5952C>A	p.Pro1984Pro	synonymous_variant	47/64			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.608

AC:

92455

AN:

152032

Hom.:

29191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.899

Gnomad SAS

AF:

0.791

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.685

AC:

171619

AN:

250590

Hom.:

60406

AF XY:

0.686

AC XY:

92913

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.446

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.894

Gnomad SAS exome

AF:

0.774

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.657

GnomAD4 exome

AF:

0.648

AC:

947212

AN:

1460686

Hom.:

311388

Cov.:

AF XY:

0.652

AC XY:

473602

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.796

Gnomad4 ASJ exome

AF:

0.630

Gnomad4 EAS exome

AF:

0.908

Gnomad4 SAS exome

AF:

0.772

Gnomad4 FIN exome

AF:

0.716

Gnomad4 NFE exome

AF:

0.628

Gnomad4 OTH exome

AF:

0.641

GnomAD4 genome

AF:

0.608

AC:

92527

AN:

152150

Hom.:

29223

Cov.:

AF XY:

0.618

AC XY:

46001

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.713

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.899

Gnomad4 SAS

AF:

0.792

Gnomad4 FIN

AF:

0.735

Gnomad4 NFE

AF:

0.625

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.621

Hom.:

55251

Bravo

AF:

0.596

Asia WGS

AF:

0.804

AC:

2794

AN:

3478

EpiCase

AF:

0.617

EpiControl

AF:

0.616

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Oct 21, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.1

DANN

Benign

0.56

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