VCV000036481.41 - ClinVar

NM_002335.4(LRP5):c.4000+9C>T

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(12)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(5); Likely benign(3)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002335.4(LRP5):c.4000+9C>T

Variation ID: 36481 Accession: VCV000036481.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.2 11: 68433847 (GRCh38) [ NCBI UCSC ] 11: 68201315 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Oct 20, 2024	Jul 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002335.4:c.4000+9C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001291902.2:c.2257+9C>T		intron variant
NC_000011.10:g.68433847C>T
NC_000011.9:g.68201315C>T
NG_015835.2:g.126208C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:68433846:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00240 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00240

1000 Genomes Project 30x 0.00265

The Genome Aggregation Database (gnomAD) 0.00389

The Genome Aggregation Database (gnomAD), exomes 0.00524

Exome Aggregation Consortium (ExAC) 0.00586

Trans-Omics for Precision Medicine (TOPMed) 0.00427

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00432

Links

ClinGen: CA201380 dbSNP: rs148685646 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
LRP5		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2064	2081

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Postmenopausal osteoporosis	Uncertain significance (1)	criteria provided, single submitter	Aug 18, 2011	RCV000030153.4
not specified	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Jun 28, 2021	RCV000175300.14
not provided	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Jul 1, 2024	RCV000949971.29
Increased bone mineral density	Benign (1)	criteria provided, single submitter	May 13, 2021	RCV002276590.4
Osteogenesis imperfecta	Benign (1)	criteria provided, single submitter	May 13, 2021	RCV002276589.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000308846.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Likely benign (Nov 07, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000226767.5 First in ClinVar: Jun 28, 2015 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LRP5 http://www.ncbi.nlm.nih.gov/vari… http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/?chr=11&from=68201315&to=68201315 Number of individuals with the variant: 2 Sex: mixed
Benign (Jun 28, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV002066261.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022
Benign (May 13, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Osteogenesis imperfecta Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002564903.1 First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022
Benign (May 13, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Increased bone mineral density Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002564678.1 First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001940230.2 First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023
Benign (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001096248.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
uncertain (Aug 18, 2011)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: curation, clinical testing	Idiopathic Osteoporosis (autosomal unknown) Affected status: unknown, yes Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000052809.2 First in ClinVar: Apr 04, 2013 Last updated: Mar 28, 2022	Comment: Converted during submission to Uncertain significance. Observation 1: Tissue: Blood Observation 2: Tissue: Blood Observation 3: Tissue: Blood Observation 4: Tissue: Blood Observation 5: Tissue: Blood Observation 6: Tissue: Blood
Likely benign (Jul 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV003916746.13 First in ClinVar: Apr 23, 2023 Last updated: Oct 20, 2024	Comment: LRP5: BS2 Number of individuals with the variant: 7
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001809301.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001919329.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001969001.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LRP5	-	-	-	-

Text-mined citations for rs148685646 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_002335.4(LRP5):c.4000+9C>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs148685646 ...