Variant rs55694948 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.4748-77T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 941,574 control chromosomes in the GnomAD database, including 12,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2660 hom., cov: 32)

Exomes 𝑓: 0.16 ( 9962 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.306

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-48465935-A-C is Benign according to our data. Variant chr15-48465935-A-C is described in ClinVar as [Benign]. Clinvar id is 1237499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48465935-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN1	NM_000138.5 link	c.4748-77T>G		intron_variant	Intron 38 of 65	ENST00000316623.10	NP_000129.3	P35555
FBN1	NM_001406716.1 link	c.4748-77T>G		intron_variant	Intron 37 of 64		NP_001393645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN1	ENST00000316623.10 link	c.4748-77T>G		intron_variant	Intron 38 of 65	1	NM_000138.5	ENSP00000325527.5		P35555

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27638

AN:

152022

Hom.:

2650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.188

GnomAD4 exome

AF:

0.155

AC:

122496

AN:

789434

Hom.:

9962

AF XY:

0.155

AC XY:

64595

AN XY:

415952

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.182

AC:

27669

AN:

152140

Hom.:

2660

Cov.:

AF XY:

0.180

AC XY:

13387

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.0822

Hom.:

106

Bravo

AF:

0.188

Asia WGS

AF:

0.239

AC:

828

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

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 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

DANN

Benign

0.37

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