Variant 15-48490366-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000138.5(FBN1):c.2855-288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,000 control chromosomes in the GnomAD database, including 23,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 23026 hom., cov: 31)

Consequence

FBN1
NM_000138.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0380

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-48490366-T-C is Benign according to our data. Variant chr15-48490366-T-C is described in ClinVar as [Benign]. Clinvar id is 680570.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN1	NM_000138.5 link	c.2855-288A>G		intron_variant		ENST00000316623.10	NP_000129.3	P35555
FBN1	NM_001406716.1 link	c.2855-288A>G		intron_variant			NP_001393645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN1	ENST00000316623.10 link	c.2855-288A>G		intron_variant		1	NM_000138.5	ENSP00000325527.5		P35555

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74843

AN:

151882

Hom.:

22960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.493

AC:

74972

AN:

152000

Hom.:

23026

Cov.:

AF XY:

0.491

AC XY:

36512

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.867

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.724

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.455

Alfa

AF:

0.327

Hom.:

11656

Bravo

AF:

0.513

Asia WGS

AF:

0.634

AC:

2202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.1

DANN

Benign

0.53

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