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NM_000527.5(LDLR):c.-4G>A AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 18, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV004013620.2

Allele description [Variation Report for NM_000527.5(LDLR):c.-4G>A]

NM_000527.5(LDLR):c.-4G>A

Genes:
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.-4G>A
HGVS:
  • NC_000019.10:g.11089545G>A
  • NG_009060.1:g.5165G>A
  • NM_000527.5:c.-4G>AMANE SELECT
  • NM_001195798.2:c.-4G>A
  • NM_001195799.2:c.-4G>A
  • NM_001195800.2:c.-4G>A
  • NM_001195803.2:c.-4G>A
  • LRG_274t1:c.-4G>A
  • LRG_274:g.5165G>A
  • NC_000019.9:g.11200221G>A
  • NM_000527.4:c.-4G>A
  • NR_163945.1:n.115C>T
Molecular consequence:
  • NM_000527.5:c.-4G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001195798.2:c.-4G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001195799.2:c.-4G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001195800.2:c.-4G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001195803.2:c.-4G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NR_163945.1:n.115C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
2

Condition(s)

Name:
Hypercholesterolemia, familial, 1
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004829836All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 18, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided108544not providedclinical testing

Citations

PubMed

Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting.

Martín-Campos JM, Plana N, Figueras R, Ibarretxe D, Caixàs A, Esteve E, Pérez A, Bueno M, Mauri M, Roig R, Martínez S, Pintó X, Masana L, Julve J, Blanco-Vaca F; Xarxa d’Unitats de Lípids i Arteriosclerosi (XULA)..

J Clin Lipidol. 2018 Nov - Dec;12(6):1452-1462. doi: 10.1016/j.jacl.2018.09.002. Epub 2018 Sep 7.

PubMed [citation]
PMID:
30293936

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 All of Us Research Program, National Institutes of Health, SCV004829836.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

This variant is located in the 5' untranslated region of the LDLR gene. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 30293936). This variant has been identified in 1/248652 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided2not providednot providednot provided

Last Updated: May 7, 2024