Variant rs55649234 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000138.5(FBN1):c.5671+28_5671+29insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,604,668 control chromosomes in the GnomAD database, including 720 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 70 hom., cov: 32)

Exomes 𝑓: 0.022 ( 650 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.379

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 -16 ACMG points.

BP6

Variant 15-48448739-G-GA is Benign according to our data. Variant chr15-48448739-G-GA is described in ClinVar as [Benign]. Clinvar id is 255301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0771 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.5671+28_5671+29insT		intron_variant		ENST00000316623.10	NP_000129.3
FBN1	NM_001406716.1 linkuse as main transcript	c.5671+28_5671+29insT		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.5671+28_5671+29insT		intron_variant		1	NM_000138.5	ENSP00000325527	P1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3319

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0834

Gnomad SAS

AF:

0.0479

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0260

GnomAD3 exomes

AF:

0.0282

AC:

6956

AN:

246962

Hom.:

186

AF XY:

0.0268

AC XY:

3588

AN XY:

133722

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.0526

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.0752

Gnomad SAS exome

AF:

0.0399

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0218

AC:

31623

AN:

1452590

Hom.:

650

Cov.:

AF XY:

0.0220

AC XY:

15878

AN XY:

722882

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.0520

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0355

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0219

AC:

3325

AN:

152078

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1720

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.0349

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0836

Gnomad4 SAS

AF:

0.0484

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.0257

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0233

Asia WGS

AF:

0.0710

AC:

246

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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