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NM_000138.4(FBN1):c.5423-4G>A

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(3);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 25, 2020
Accession:
VCV000237098.8
Variation ID:
237098
Description:
single nucleotide variant
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NM_000138.4(FBN1):c.5423-4G>A

Allele ID
242065
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q21.1
Genomic location
15: 48452688 (GRCh38) GRCh38 UCSC
15: 48744885 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.48452688C>T
NC_000015.9:g.48744885C>T
LRG_778t1:c.5423-4G>A
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000015.10:48452687:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (T)

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00013
Exome Aggregation Consortium (ExAC) 0.00013
1000 Genomes Project 0.00060
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00042
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054
Links
ClinGen: CA054949
dbSNP: rs377036485
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, single submitter Mar 8, 2017 RCV000277311.4
Likely benign 1 criteria provided, single submitter Jul 28, 2019 RCV000617244.1
Uncertain significance 1 criteria provided, single submitter May 2, 2016 RCV000726081.3
Likely benign 1 criteria provided, single submitter Nov 25, 2020 RCV001089035.2
Benign 1 criteria provided, single submitter Dec 31, 2018 RCV001186933.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FBN1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
4793 4888

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Mar 08, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000522931.4
Submitted: (Mar 26, 2018)
Evidence details
Comment:
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 … (more)
Uncertain significance
(May 02, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000341793.4
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Benign
(Dec 31, 2018)
criteria provided, single submitter
Method: clinical testing
Familial thoracic aortic aneurysm and aortic dissection
Allele origin: germline
Color Health, Inc
Accession: SCV001353545.1
Submitted: (May 19, 2020)
Evidence details
Likely benign
(Jul 28, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000738789.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Likely benign
(Nov 25, 2020)
criteria provided, single submitter
Method: clinical testing
Marfan syndrome
Familial thoracic aortic aneurysm and aortic dissection
Allele origin: germline
Invitae
Accession: SCV000283637.5
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(Jan 22, 2020)
no assertion criteria provided
Method: curation
Not Specified
Allele origin: germline
Broad Institute Rare Disease Group, Broad Institute
Accession: SCV001422579.1
Submitted: (Mar 09, 2020)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
The c.5423-4G>A variant in FBN1 has not been previously reported in individuals with Marfan Syndrome but has been reported as likely benign and a VUS … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Text-mined citations for rs377036485...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021