15-48487034-GTAAAA-G

Variant summary

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

The NM_000138.5(FBN1):​c.3589+36_3589+40del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,279,136 control chromosomes in the GnomAD database, including 17,597 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2094 hom., cov: 29)
Exomes 𝑓: 0.15 ( 15503 hom. )

Consequence

FBN1
NM_000138.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 15-48487034-GTAAAA-G is Benign according to our data. Variant chr15-48487034-GTAAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 255294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48487034-GTAAAA-G is described in Lovd as [Benign]. Variant chr15-48487034-GTAAAA-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBN1NM_000138.5 linkuse as main transcriptc.3589+36_3589+40del intron_variant ENST00000316623.10 NP_000129.3
FBN1NM_001406716.1 linkuse as main transcriptc.3589+36_3589+40del intron_variant NP_001393645.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBN1ENST00000316623.10 linkuse as main transcriptc.3589+36_3589+40del intron_variant 1 NM_000138.5 ENSP00000325527 P1

Frequencies

GnomAD3 genomes
AF:
0.164
AC:
24574
AN:
150246
Hom.:
2086
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.168
Gnomad AMI
AF:
0.289
Gnomad AMR
AF:
0.175
Gnomad ASJ
AF:
0.0522
Gnomad EAS
AF:
0.349
Gnomad SAS
AF:
0.151
Gnomad FIN
AF:
0.199
Gnomad MID
AF:
0.0791
Gnomad NFE
AF:
0.145
Gnomad OTH
AF:
0.156
GnomAD3 exomes
AF:
0.175
AC:
14975
AN:
85474
Hom.:
1542
AF XY:
0.169
AC XY:
8044
AN XY:
47730
show subpopulations
Gnomad AFR exome
AF:
0.235
Gnomad AMR exome
AF:
0.203
Gnomad ASJ exome
AF:
0.0567
Gnomad EAS exome
AF:
0.371
Gnomad SAS exome
AF:
0.141
Gnomad FIN exome
AF:
0.200
Gnomad NFE exome
AF:
0.154
Gnomad OTH exome
AF:
0.164
GnomAD4 exome
AF:
0.153
AC:
172360
AN:
1128774
Hom.:
15503
AF XY:
0.153
AC XY:
85461
AN XY:
558522
show subpopulations
Gnomad4 AFR exome
AF:
0.177
Gnomad4 AMR exome
AF:
0.206
Gnomad4 ASJ exome
AF:
0.0633
Gnomad4 EAS exome
AF:
0.413
Gnomad4 SAS exome
AF:
0.144
Gnomad4 FIN exome
AF:
0.215
Gnomad4 NFE exome
AF:
0.142
Gnomad4 OTH exome
AF:
0.155
GnomAD4 genome
AF:
0.164
AC:
24615
AN:
150362
Hom.:
2094
Cov.:
29
AF XY:
0.167
AC XY:
12295
AN XY:
73410
show subpopulations
Gnomad4 AFR
AF:
0.168
Gnomad4 AMR
AF:
0.175
Gnomad4 ASJ
AF:
0.0522
Gnomad4 EAS
AF:
0.349
Gnomad4 SAS
AF:
0.152
Gnomad4 FIN
AF:
0.199
Gnomad4 NFE
AF:
0.145
Gnomad4 OTH
AF:
0.155

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, flagged submissionclinical testingGeneDxJun 14, 2013The variant is found in TAAD panel(s). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -

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.

Other links and lift over

dbSNP: rs72158035; hg19: chr15-48779231; API