U.S. flag

An official website of the United States government

NM_001079866.2(BCS1L):c.-49-539T>A AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 18, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_001079866.2(BCS1L):c.-49-539T>A]


BCS1L:BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000002.12:g.218660400T>A
  • NG_008018.1:g.5745T>A
  • NG_033099.1:g.4141A>T
  • NM_001079866.2:c.-49-539T>AMANE SELECT
  • NM_001257342.2:c.-50+234T>A
  • NM_001257343.2:c.-50+182T>A
  • NM_001257344.2:c.-49-539T>A
  • NM_001318836.2:c.-41+657T>A
  • NM_001320717.2:c.-71T>A
  • NM_001371443.1:c.-71T>A
  • NM_001371444.1:c.-71T>A
  • NM_001371446.1:c.-398T>A
  • NM_001371447.1:c.-31-557T>A
  • NM_001371448.1:c.-71T>A
  • NM_001371449.1:c.-71T>A
  • NM_001371450.1:c.-71T>A
  • NM_001371451.1:c.-389T>A
  • NM_001371452.1:c.-42+657T>A
  • NM_001371453.1:c.-1064T>A
  • NM_001371454.1:c.-547T>A
  • NM_001371455.1:c.-525-539T>A
  • NM_001371456.1:c.-526+234T>A
  • NM_001374085.1:c.-588T>A
  • NM_001374086.1:c.-1064T>A
  • NM_004328.5:c.-50+155T>A
  • LRG_539t1:c.-50+155T>A
  • LRG_539:g.5745T>A
  • NC_000002.11:g.219525123T>A
  • NM_004328.4:c.-50+155T>A
  • NR_163955.1:n.425T>A
dbSNP: rs386833855
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001320717.2:c.-71T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371443.1:c.-71T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371444.1:c.-71T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371446.1:c.-398T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371448.1:c.-71T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371449.1:c.-71T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371450.1:c.-71T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371451.1:c.-389T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371453.1:c.-1064T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371454.1:c.-547T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001374085.1:c.-588T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001374086.1:c.-1064T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001079866.2:c.-49-539T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001257342.2:c.-50+234T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001257343.2:c.-50+182T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001257344.2:c.-49-539T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001318836.2:c.-41+657T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371447.1:c.-31-557T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371452.1:c.-42+657T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371455.1:c.-525-539T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371456.1:c.-526+234T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004328.5:c.-50+155T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NR_163955.1:n.425T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


none provided
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jun 18, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L.

Visapää I, Fellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V, Payne GS, Makarow M, Van Coster R, Taylor RW, Turnbull DM, Suomalainen A, Peltonen L.

Am J Hum Genet. 2002 Oct;71(4):863-76. Epub 2002 Sep 5.

PubMed [citation]

BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency.

Lynn AM, King RI, Mackay RJ, Florkowski CM, Wilson CJ.

Ann Clin Biochem. 2012 Mar;49(Pt 2):201-3. doi: 10.1258/acb.2011.011180. Epub 2012 Jan 25.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004293969.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 56411). This variant is also known as c.-588T>A. This variant has been observed in individual(s) with GRACILE syndrome (PMID: 12215968, 22277166). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the BCS1L gene. It does not change the encoded amino acid sequence of the BCS1L protein.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024