Variant 19-8094478-G-T 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.5873C>A(p.Pro1958His) variant causes a missense change. The variant allele was found at a frequency of 0.422 in 1,612,292 control chromosomes in the GnomAD database, including 149,915 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 0.39 ( 12817 hom., cov: 34)

Exomes 𝑓: 0.43 ( 137098 hom. )

Consequence

FBN3
ENST00000600128.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.29

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=2.5079229E-5).

BP6

Variant 19-8094478-G-T is Benign according to our data. Variant chr19-8094478-G-T is described in ClinVar as [Benign]. Clinvar id is 1297917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8094478-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 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.5873C>A	p.Pro1958His	missense_variant	47/64	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.5873C>A	p.Pro1958His	missense_variant	47/64	1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6 linkuse as main transcript	c.5873C>A	p.Pro1958His	missense_variant	46/63	1		ENSP00000270509
FBN3	ENST00000601739.5 linkuse as main transcript	c.5873C>A	p.Pro1958His	missense_variant	47/64	1		ENSP00000472324
FBN3	ENST00000651877.1 linkuse as main transcript	c.5999C>A	p.Pro2000His	missense_variant	47/64			ENSP00000498507	P1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59258

AN:

152012

Hom.:

12801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.372

GnomAD3 exomes

AF:

0.468

AC:

116676

AN:

249542

Hom.:

29469

AF XY:

0.466

AC XY:

62877

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.726

Gnomad SAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.440

GnomAD4 exome

AF:

0.425

AC:

621061

AN:

1460162

Hom.:

137098

Cov.:

AF XY:

0.429

AC XY:

311466

AN XY:

726358

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.707

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.514

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.390

AC:

59296

AN:

152130

Hom.:

12817

Cov.:

AF XY:

0.402

AC XY:

29899

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.730

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.395

Hom.:

30845

Bravo

AF:

0.376

TwinsUK

AF:

0.406

AC:

1504

ALSPAC

AF:

0.413

AC:

1592

ESP6500AA

AF:

0.235

AC:

1034

ESP6500EA

AF:

0.387

AC:

3332

ExAC

AF:

0.455

AC:

55211

Asia WGS

AF:

0.600

AC:

2083

AN:

3478

EpiCase

AF:

0.382

EpiControl

AF:

0.381

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;T;T

Eigen

Benign

0.021

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

.;.;T

MetaRNN

Benign

0.000025

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

0.000058

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.8

.;D;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.010

.;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.96

D;D;D

Vest4

0.36

MPC

0.77

ClinPred

0.060

GERP RS

1.4

Varity_R

0.60

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