Variant rs55699652 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 ENST00000316623.10(FBN1):c.1147+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,613,280 control chromosomes in the GnomAD database, including 1,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 213 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1677 hom. )

Consequence

FBN1
ENST00000316623.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.574

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=-0.86).

BP6

Variant 15-48520631-T-C is Benign according to our data. Variant chr15-48520631-T-C is described in ClinVar as [Benign]. Clinvar id is 255285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48520631-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.1147+28A>G		intron_variant		ENST00000316623.10	NP_000129.3
FBN1	NM_001406716.1 linkuse as main transcript	c.1147+28A>G		intron_variant			NP_001393645.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
FBN1	ENST00000316623.10 linkuse as main transcript	c.1147+28A>G	intron_variant	1	NM_000138.5	ENSP00000325527	P1
FBN1	ENST00000559133.6 linkuse as main transcript	c.1147+28A>G	intron_variant, NMD_transcript_variant	1		ENSP00000453958
FBN1	ENST00000537463.6 linkuse as main transcript	c.636+17080A>G	intron_variant, NMD_transcript_variant	5		ENSP00000440294
FBN1	ENST00000674301.2 linkuse as main transcript	c.1147+28A>G	intron_variant, NMD_transcript_variant			ENSP00000501333

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2570

AN:

152132

Hom.:

211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0327

AC:

8198

AN:

250740

Hom.:

666

AF XY:

0.0295

AC XY:

3999

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.0718

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.0283

Gnomad FIN exome

AF:

0.00385

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.0208

GnomAD4 exome

AF:

0.0124

AC:

18065

AN:

1461030

Hom.:

1677

Cov.:

AF XY:

0.0124

AC XY:

9004

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.00795

Gnomad4 AMR exome

AF:

0.0694

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.000767

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0169

AC:

2579

AN:

152250

Hom.:

213

Cov.:

AF XY:

0.0196

AC XY:

1461

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00864

Gnomad4 AMR

AF:

0.0449

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.0292

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.123

AC:

426

AN:

3478

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.6

DANN

Benign

0.65

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