chr15-48463253-T-TA

Position:

chr15-48463253-T-TA

Variant summary

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

The ENST00000316623.10(FBN1):c.5066-14_5066-13insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,609,614 control chromosomes in the GnomAD database, including 618 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 64 hom., cov: 33)

Exomes 𝑓: 0.016 ( 554 hom. )

Consequence

FBN1
ENST00000316623.10 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14O:1

Conservation

PhyloP100: -0.716

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 15-48463253-T-TA is Benign according to our data. Variant chr15-48463253-T-TA is described in ClinVar as [Benign]. Clinvar id is 178599.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.5066-14_5066-13insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000316623.10	NP_000129.3
FBN1	NM_001406716.1 linkuse as main transcript	c.5066-14_5066-13insT		splice_polypyrimidine_tract_variant, 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.5066-14_5066-13insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000138.5	ENSP00000325527	P1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3471

AN:

151366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.00780

Gnomad EAS

AF:

0.0835

Gnomad SAS

AF:

0.0475

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00969

Gnomad OTH

AF:

0.0231

GnomAD3 exomes

AF:

0.0261

AC:

6549

AN:

250872

Hom.:

180

AF XY:

0.0248

AC XY:

3358

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.0306

Gnomad AMR exome

AF:

0.0517

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.0764

Gnomad SAS exome

AF:

0.0400

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0252

GnomAD4 exome

AF:

0.0158

AC:

23076

AN:

1458132

Hom.:

554

Cov.:

AF XY:

0.0162

AC XY:

11777

AN XY:

725562

show subpopulations

Gnomad4 AFR exome

AF:

0.0323

Gnomad4 AMR exome

AF:

0.0509

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0354

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.00903

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0230

AC:

3482

AN:

151482

Hom.:

Cov.:

AF XY:

0.0243

AC XY:

1798

AN XY:

73998

show subpopulations

Gnomad4 AFR

AF:

0.0323

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.00780

Gnomad4 EAS

AF:

0.0837

Gnomad4 SAS

AF:

0.0480

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.00969

Gnomad4 OTH

AF:

0.0228

Bravo

AF:

0.0251

Asia WGS

AF:

0.0720

AC:

252

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3Other:1

not provided, no classification provided	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 05, 2014	5066-14_5066-13insT in intron 40 of FBN1: This variant is not expected to have clinical significance because it has been identified in 1% (85/8254) of European American chromosomes and 2.89% (123/4264) of African American chromosomes by the NHLBI Exome Sequencing Project, and it is not located within the splice consensus sequence. (http://evs.gs.washington.edu/EVS/; dbSNP rs3833018). -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Apr 08, 2018	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 16, 2021	- -

Ectopia lentis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Marfan syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Stiff skin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Weill-Marchesani syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Geleophysic dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Acromicric dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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