rs2306862

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002335.4(LRP5):c.2220C>T(p.Asn740Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,820 control chromosomes in the GnomAD database, including 19,522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1352 hom., cov: 31)

Exomes 𝑓: 0.15 ( 18170 hom. )

Consequence

LRP5
NM_002335.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: 0.276

Variant links:

Genes affected

LRP5 (HGNC:6697): (LDL receptor related protein 5) This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

LRP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 11-68410042-C-T is Benign according to our data. Variant chr11-68410042-C-T is described in ClinVar as [Benign]. Clinvar id is 193639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68410042-C-T is described in Lovd as [Likely_pathogenic]. Variant chr11-68410042-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.276 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP5	NM_002335.4 link	c.2220C>T	p.Asn740Asn	synonymous_variant	Exon 10 of 23	ENST00000294304.12	NP_002326.2	O75197

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP5	ENST00000294304.12 link	c.2220C>T	p.Asn740Asn	synonymous_variant	Exon 10 of 23	1	NM_002335.4	ENSP00000294304.6	O75197
LRP5	ENST00000529993.5 link	n.*826C>T		non_coding_transcript_exon_variant	Exon 10 of 23	1		ENSP00000436652.1	E9PHY1
LRP5	ENST00000529993.5 link	n.*826C>T		3_prime_UTR_variant	Exon 10 of 23	1		ENSP00000436652.1	E9PHY1
LRP5	ENST00000528714.1 link	n.14C>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

18011

AN:

152022

Hom.:

1352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0468

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.0841

Gnomad FIN

AF:

0.0429

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.136

AC:

34275

AN:

251274

Hom.:

2709

AF XY:

0.133

AC XY:

18022

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0464

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.199

Gnomad SAS exome

AF:

0.0809

Gnomad FIN exome

AF:

0.0472

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.152

AC:

222751

AN:

1461680

Hom.:

18170

Cov.:

AF XY:

0.150

AC XY:

109128

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.0815

Gnomad4 FIN exome

AF:

0.0503

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.118

AC:

18015

AN:

152140

Hom.:

1352

Cov.:

AF XY:

0.114

AC XY:

8461

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0467

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.0843

Gnomad4 FIN

AF:

0.0429

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.152

Hom.:

3199

Bravo

AF:

0.132

Asia WGS

AF:

0.125

AC:

436

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 01, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22511589, 17505772, 16115379) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 24, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta

Benign:1

Jul 18, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Increased bone mineral density

Benign:1

Mar 19, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bone mineral density quantitative trait locus 1

Other:1

Jan 01, 2004

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.6

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over