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NM_000527.5(LDLR):c.1545C>T (p.Asn515=) AND not specified

Germline classification:
Benign (1 submission)
Last evaluated:
Jun 3, 2019
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:
RCV001193181.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1545C>T (p.Asn515=)]

NM_000527.5(LDLR):c.1545C>T (p.Asn515=)

Gene:
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.1545C>T (p.Asn515=)
HGVS:
  • NC_000019.10:g.11113721C>T
  • NG_009060.1:g.29341C>T
  • NM_000527.5:c.1545C>TMANE SELECT
  • NM_001195798.2:c.1545C>T
  • NM_001195799.2:c.1422C>T
  • NM_001195800.2:c.1041C>T
  • NM_001195803.2:c.1164C>T
  • NP_000518.1:p.Asn515=
  • NP_000518.1:p.Asn515=
  • NP_001182727.1:p.Asn515=
  • NP_001182728.1:p.Asn474=
  • NP_001182729.1:p.Asn347=
  • NP_001182732.1:p.Asn388=
  • LRG_274t1:c.1545C>T
  • LRG_274:g.29341C>T
  • LRG_274p1:p.Asn515=
  • NC_000019.9:g.11224397C>T
  • NM_000527.4:c.1545C>T
  • c.1545C>T
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000210; dbSNP: rs147896205
NCBI 1000 Genomes Browser:
rs147896205
Molecular consequence:
  • NM_000527.5:c.1545C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195798.2:c.1545C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195799.2:c.1422C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195800.2:c.1041C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195803.2:c.1164C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001361869Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Benign
(Jun 3, 2019) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

High sensitivity of the single-strand conformation polymorphism method for detecting sequence variations in the low-density lipoprotein receptor gene validated by DNA sequencing.

Jensen HK, Jensen LG, Hansen PS, Faergeman O, Gregersen N.

Clin Chem. 1996 Aug;42(8 Pt 1):1140-6.

PubMed [citation]
PMID:
8697568

The genetic spectrum of familial hypercholesterolemia in south-eastern Poland.

Sharifi M, Walus-Miarka M, Idzior-WaluĊ› B, Malecki MT, Sanak M, Whittall R, Li KW, Futema M, Humphries SE.

Metabolism. 2016 Mar;65(3):48-53. doi: 10.1016/j.metabol.2015.10.018. Epub 2015 Nov 10.

PubMed [citation]
PMID:
26892515
PMCID:
PMC4766367

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361869.1

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

Description

Variant summary: LDLR c.1545C>T alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.002 in 251392 control chromosomes in the gnomAD database, including 7 homozygotes. The observed variant frequency is approximately 1.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in LDLR causing Familial Hypercholesterolemia phenotype (0.0013), strongly suggesting that the variant is benign. c.1545C>T has been reported in the literature in sequencing studies of individuals affected with Familial Hypercholesterolemia (Sharifi_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=3)/likely benign (n=1). Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Oct 20, 2024