rs140605

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000138.5(FBN1):c.2168-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,553,576 control chromosomes in the GnomAD database, including 60,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10638 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50161 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.10

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:

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 (BayesDel_noAF=-0.9).

BP6

Variant 15-48497437-T-C is Benign according to our data. Variant chr15-48497437-T-C is described in ClinVar as [Benign]. Clinvar id is 255288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48497437-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN1	NM_000138.5 link	c.2168-46A>G		intron_variant	Intron 18 of 65	ENST00000316623.10	NP_000129.3	P35555
FBN1	NM_001406716.1 link	c.2168-46A>G		intron_variant	Intron 17 of 64		NP_001393645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN1	ENST00000316623.10 link	c.2168-46A>G		intron_variant	Intron 18 of 65	1	NM_000138.5	ENSP00000325527.5		P35555

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52382

AN:

151850

Hom.:

10610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.279

AC:

67458

AN:

242142

Hom.:

10365

AF XY:

0.270

AC XY:

35538

AN XY:

131618

show subpopulations

Gnomad AFR exome

AF:

0.593

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.259

AC:

363291

AN:

1401608

Hom.:

50161

Cov.:

AF XY:

0.257

AC XY:

179881

AN XY:

700794

show subpopulations

Gnomad4 AFR exome

AF:

0.587

Gnomad4 AMR exome

AF:

0.265

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.345

AC:

52465

AN:

151968

Hom.:

10638

Cov.:

AF XY:

0.343

AC XY:

25481

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.357

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.287

Hom.:

1587

Bravo

AF:

0.359

Asia WGS

AF:

0.317

AC:

1103

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

DANN

Benign

0.68

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