NM_000527.4(LDLR):c.-120C>T AND Familial hypercholesterolemia

Clinical significance:Uncertain significance (Last evaluated: Jun 13, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001190436.1

Allele description [Variation Report for NM_000527.4(LDLR):c.-120C>T]

NM_000527.4(LDLR):c.-120C>T

Genes:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.4(LDLR):c.-120C>T
HGVS:
  • NC_000019.10:g.11089429C>T
  • NG_009060.1:g.5049C>T
  • NG_009060.1:g.5049C>T
  • LRG_274t1:c.-120C>T
  • LRG_274:g.5049C>T
  • NC_000019.9:g.11200105C>T
  • NC_000019.9:g.11200105C>T
  • NM_000527.4:c.-120C>T
  • NR_163945.1:n.231G>A
  • c.-120C>T
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001115; dbSNP: rs875989886
NCBI 1000 Genomes Browser:
rs875989886
Molecular consequence:
  • NR_163945.1:n.231G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Familial hypercholesterolemia (FH)
Identifiers:
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001357925Color Health, Inccriteria provided, single submitter
Uncertain significance
(Jun 13, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Description

This variant (also known as -27C>T , counting from the transcription start site) changes a conserved nucleotide in the promoter region of the LDLR gene. An experimental functional study has shown that this variant abolishes the promoter activity in a luciferase-based assay performed in HepG2 cells (PMID: 15303010). However, this variant has shown no significant impact on the promoter activity in a similar luciferase-based assay performed in Huh7 cells (PMID: 25248394). This variant has been reported in 3 or more Czech individuals affected with familial hypercholesterolemia (PMID: 15303010, 21310417, 22698793). This variant has also been reported in a 70-year old patient with very low Dutch Lipid Clinical Network-score (PMID: 29974534). This variant has been identified in 1/31400 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Due to the conflicting functional study results and insufficient clinical evidence, the role of this variant in disease cannot be determined conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

SCV001357925

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Health, Inc, SCV001357925.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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