11-68312746-CGCTGCTGCTGCTGCT-CGCTGCT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002335.4(LRP5):c.52_60delCTGCTGCTG(p.Leu18_Leu20del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,061,146 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 5 hom., cov: 28)

Exomes 𝑓: 0.014 ( 70 hom. )

Consequence

LRP5
NM_002335.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:8

Conservation

PhyloP100: 0.190

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 -16 ACMG points.

BP6

Variant 11-68312746-CGCTGCTGCT-C is Benign according to our data. Variant chr11-68312746-CGCTGCTGCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 204504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68312746-CGCTGCTGCT-C is described in Lovd as [Benign]. Variant chr11-68312746-CGCTGCTGCT-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00902 (1303/144404) while in subpopulation NFE AF= 0.0137 (894/65172). AF 95% confidence interval is 0.013. There are 5 homozygotes in gnomad4. There are 584 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP5	NM_002335.4 link	c.52_60delCTGCTGCTG	p.Leu18_Leu20del	conservative_inframe_deletion	Exon 1 of 23	ENST00000294304.12	NP_002326.2	O75197

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12 link	c.52_60delCTGCTGCTG	p.Leu18_Leu20del	conservative_inframe_deletion	Exon 1 of 23	1	NM_002335.4	ENSP00000294304.6		O75197
LRP5	ENST00000529993.5 link	n.52_60delCTGCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 23	1		ENSP00000436652.1		E9PHY1

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1300

AN:

144318

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00371

Gnomad AMI

AF:

0.00340

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00446

Gnomad EAS

AF:

0.000809

Gnomad SAS

AF:

0.00168

Gnomad FIN

AF:

0.00383

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00901

GnomAD3 exomes

AF:

0.000491

AC:

AN:

16308

Hom.:

AF XY:

0.000812

AC XY:

AN XY:

9856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000681

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0137

AC:

12529

AN:

916742

Hom.:

AF XY:

0.0134

AC XY:

5870

AN XY:

438388

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00361

Gnomad4 ASJ exome

AF:

0.00332

Gnomad4 EAS exome

AF:

0.000171

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.00979

GnomAD4 genome

AF:

0.00902

AC:

1303

AN:

144404

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

584

AN XY:

70312

show subpopulations

Gnomad4 AFR

AF:

0.00377

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.00446

Gnomad4 EAS

AF:

0.000812

Gnomad4 SAS

AF:

0.00169

Gnomad4 FIN

AF:

0.00383

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00893

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LRP5: BS1 -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21151595, 12579474, 16234968, 19177549) -

Autosomal dominant polycystic liver disease

Uncertain:1

Sep 01, 2021

Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Osteogenesis imperfecta

Benign:1

Mar 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 16, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Increased bone mineral density

Benign:1

Mar 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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