NM_000138.5(FBN1):c.79G>A (p.Ala27Thr) AND not provided

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Sep 23, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000588579.16

Allele description [Variation Report for NM_000138.5(FBN1):c.79G>A (p.Ala27Thr)]

NM_000138.5(FBN1):c.79G>A (p.Ala27Thr)

Genes:

LOC130057019:ATAC-STARR-seq lymphoblastoid silent region 6417 [Gene]
FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.79G>A (p.Ala27Thr)

Other names:

p.A27T:GCC>ACC; NM_000138.5(FBN1):c.79G>A

HGVS:

NC_000015.10:g.48644691C>T
NG_008805.2:g.6098G>A
NM_000138.5:c.79G>AMANE SELECT
NP_000129.3:p.Ala27Thr
NP_000129.3:p.Ala27Thr
LRG_778t1:c.79G>A
LRG_778:g.6098G>A
LRG_778p1:p.Ala27Thr
NC_000015.9:g.48936888C>T
NM_000138.4:c.79G>A

Protein change:

A27T

Links:

dbSNP: rs25397

NCBI 1000 Genomes Browser:

rs25397

Molecular consequence:

NM_000138.5:c.79G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000233706	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Sep 23, 2020)	germline	clinical testing	Citation Link,
SCV000695613	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jul 20, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19839986, 26272055, 16835936 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001798110	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001808335	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001964661	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome.

Hung CC, Lin SY, Lee CN, Cheng HY, Lin SP, Chen MR, Chen CP, Chang CH, Lin CY, Yu CC, Chiu HH, Cheng WF, Ho HN, Niu DM, Su YN.

Ann Hum Genet. 2009 Nov;73(Pt 6):559-67. doi: 10.1111/j.1469-1809.2009.00545.x.

PubMed [citation]

PMID:: 19839986

Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD.

Guo J, Cai L, Jia L, Li X, Xi X, Zheng S, Liu X, Piao C, Liu T, Sun Z, Cai T, Du J.

Sci Rep. 2015 Aug 14;5:13115. doi: 10.1038/srep13115.

PubMed [citation]

PMID:: 26272055
PMCID:: PMC4536522

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000233706.15

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is associated with the following publications: (PMID: 26272055, 19839986, 16835936)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695613.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: The FBN1 c.79G>A (p.Ala27Thr) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome. However, these predictions have yet to be functionally assessed. This variant was found in 60/124386 control chromosomes, predominantly observed in the East Asian cohort at a frequency of 0.00601 (52/8652). This frequency is about 53 times the estimated maximal expected allele frequency of a pathogenic FBN1 variant (0.0001125), suggesting this is likely a benign polymorphism found primarily in population(s) of East Asia. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001798110.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808335.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001964661.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 11, 2025

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