Variant rs531498242 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_000138.5(FBN1):c.3589+40_3589+41insTTTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,280,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00

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 Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00127 (191/150480) while in subpopulation AFR AF= 0.00362 (148/40890). AF 95% confidence interval is 0.00314. There are 0 homozygotes in gnomad4. There are 92 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 191 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN1	NM_000138.5 linkuse as main transcript	c.3589+40_3589+41insTTTTA		intron_variant		ENST00000316623.10
FBN1	NM_001406716.1 linkuse as main transcript	c.3589+40_3589+41insTTTTA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN1	ENST00000316623.10 linkuse as main transcript	c.3589+40_3589+41insTTTTA		intron_variant		1	NM_000138.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

190

AN:

150364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00358

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000595

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00127

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000384

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.000175

AC:

AN:

85474

Hom.:

AF XY:

0.000189

AC XY:

AN XY:

47730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.000205

Gnomad EAS exome

AF:

0.000175

Gnomad SAS exome

AF:

0.000145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.000473

GnomAD4 exome

AF:

0.000219

AC:

248

AN:

1130198

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

121

AN XY:

559152

show subpopulations

Gnomad4 AFR exome

AF:

0.00270

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.000152

Gnomad4 EAS exome

AF:

0.000187

Gnomad4 SAS exome

AF:

0.000370

Gnomad4 FIN exome

AF:

0.000100

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.000235

GnomAD4 genome

AF:

0.00127

AC:

191

AN:

150480

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

73464

show subpopulations

Gnomad4 AFR

AF:

0.00362

Gnomad4 AMR

AF:

0.000594

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.00106

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000384

Gnomad4 OTH

AF:

0.000481

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Marfan syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 18, 2011

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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