Variant 15-48444487-A-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 NM_000138.5(FBN1):c.6037+54T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,604,964 control chromosomes in the GnomAD database, including 434,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34483 hom., cov: 32)

Exomes 𝑓: 0.74 ( 400211 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0670

Variant links:

Genes affected

FBN1 (HGNC:3603): (fibrillin 1) This gene encodes a member of the fibrillin family of proteins. The encoded preproprotein is proteolytically processed to generate two proteins including the extracellular matrix component fibrillin-1 and the protein hormone asprosin. Fibrillin-1 is an extracellular matrix glycoprotein that serves as a structural component of calcium-binding microfibrils. These microfibrils provide force-bearing structural support in elastic and nonelastic connective tissue throughout the body. Asprosin, secreted by white adipose tissue, has been shown to regulate glucose homeostasis. Mutations in this gene are associated with Marfan syndrome and the related MASS phenotype, as well as ectopia lentis syndrome, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome and neonatal progeroid syndrome. [provided by RefSeq, Apr 2016]

FBN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-48444487-A-T is Benign according to our data. Variant chr15-48444487-A-T is described in ClinVar as [Benign]. Clinvar id is 1273419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48444487-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN1	NM_000138.5 linkuse as main transcript	c.6037+54T>A		intron_variant		ENST00000316623.10	NP_000129.3
FBN1	NM_001406716.1 linkuse as main transcript	c.6037+54T>A		intron_variant			NP_001393645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN1	ENST00000316623.10 linkuse as main transcript	c.6037+54T>A		intron_variant		1	NM_000138.5	ENSP00000325527	P1

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100588

AN:

151924

Hom.:

34487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.801

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.752

Gnomad OTH

AF:

0.686

GnomAD4 exome

AF:

0.739

AC:

1074261

AN:

1452922

Hom.:

400211

AF XY:

0.742

AC XY:

536332

AN XY:

723256

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.733

Gnomad4 ASJ exome

AF:

0.789

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.776

Gnomad4 FIN exome

AF:

0.726

Gnomad4 NFE exome

AF:

0.752

Gnomad4 OTH exome

AF:

0.724

GnomAD4 genome

AF:

0.662

AC:

100608

AN:

152042

Hom.:

34483

Cov.:

AF XY:

0.663

AC XY:

49272

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.466

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.801

Gnomad4 EAS

AF:

0.596

Gnomad4 SAS

AF:

0.754

Gnomad4 FIN

AF:

0.735

Gnomad4 NFE

AF:

0.752

Gnomad4 OTH

AF:

0.687

Alfa

AF:

0.699

Hom.:

4735

Bravo

AF:

0.649

Asia WGS

AF:

0.654

AC:

2274

AN:

3478

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	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.62

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