Variant rs3825962 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.6497-23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,612,150 control chromosomes in the GnomAD database, including 1,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.035 ( 289 hom., cov: 32)

Exomes 𝑓: 0.016 ( 1510 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0800

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

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-48434736-C-G is Benign according to our data. Variant chr15-48434736-C-G is described in ClinVar as [Benign]. Clinvar id is 255304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48434736-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN1	NM_000138.5 linkuse as main transcript	c.6497-23G>C		intron_variant		ENST00000316623.10
FBN1	NM_001406716.1 linkuse as main transcript	c.6497-23G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN1	ENST00000316623.10 linkuse as main transcript	c.6497-23G>C		intron_variant		1	NM_000138.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5317

AN:

152078

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0561

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0404

AC:

10146

AN:

250882

Hom.:

739

AF XY:

0.0355

AC XY:

4815

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.0665

Gnomad AMR exome

AF:

0.0808

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.00463

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0163

AC:

23796

AN:

1459954

Hom.:

1510

Cov.:

AF XY:

0.0159

AC XY:

11559

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.0677

Gnomad4 AMR exome

AF:

0.0785

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.00267

Gnomad4 NFE exome

AF:

0.00380

Gnomad4 OTH exome

AF:

0.0277

GnomAD4 genome

AF:

0.0350

AC:

5333

AN:

152196

Hom.:

289

Cov.:

AF XY:

0.0360

AC XY:

2682

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0623

Gnomad4 AMR

AF:

0.0564

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.0351

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0412

Asia WGS

AF:

0.135

AC:

467

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

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

DANN

Benign

0.62

BranchPoint Hunter

2.0

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