rs607887

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002335.4(LRP5):c.3638-82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,581,846 control chromosomes in the GnomAD database, including 83,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10349 hom., cov: 31)

Exomes 𝑓: 0.32 ( 73636 hom. )

Consequence

LRP5
NM_002335.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.07

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

bone mineral density quantitative trait locus 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
LRP5-related exudative vitreoretinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
osteoporosis-pseudoglioma syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
exudative vitreoretinopathy 4
Inheritance: Unknown, AD, SD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
autosomal dominant osteosclerosis, Worth type
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
polycystic liver disease 4 with or without kidney cysts
Inheritance: AD Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
autosomal dominant osteopetrosis 1
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
exudative vitreoretinopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hyperostosis corticalis generalisata
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteosclerosis-developmental delay-craniosynostosis syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
polycystic liver disease 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LRP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-68429493-C-T is Benign according to our data. Variant chr11-68429493-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002335.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP5	NM_002335.4	MANE Select	c.3638-82C>T		intron	N/A	NP_002326.2	O75197
	LRP5	NM_001291902.2		c.1895-82C>T		intron	N/A	NP_001278831.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRP5	ENST00000294304.12	TSL:1 MANE Select	c.3638-82C>T	intron	N/A	ENSP00000294304.6	O75197
LRP5	ENST00000529993.5	TSL:1	n.*2244-82C>T	intron	N/A	ENSP00000436652.1	E9PHY1
LRP5	ENST00000909991.1		c.3701-82C>T	intron	N/A	ENSP00000580050.1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53221

AN:

151960

Hom.:

10324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.316

AC:

451234

AN:

1429766

Hom.:

73636

AF XY:

0.312

AC XY:

222331

AN XY:

712940

show subpopulations

African (AFR)

AF:

0.503

AC:

16532

AN:

32884

American (AMR)

AF:

0.296

AC:

13199

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

8220

AN:

25962

East Asian (EAS)

AF:

0.317

AC:

12504

AN:

39502

South Asian (SAS)

AF:

0.217

AC:

18502

AN:

85190

European-Finnish (FIN)

AF:

0.141

AC:

7313

AN:

51874

Middle Eastern (MID)

AF:

0.410

AC:

1735

AN:

4236

European-Non Finnish (NFE)

AF:

0.326

AC:

353962

AN:

1086314

Other (OTH)

AF:

0.325

AC:

19267

AN:

59284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

15261

30523

45784

61046

76307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11452

22904

34356

45808

57260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.350

AC:

53292

AN:

152080

Hom.:

10349

Cov.:

AF XY:

0.339

AC XY:

25221

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.493

AC:

20433

AN:

41450

American (AMR)

AF:

0.331

AC:

5063

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1065

AN:

3470

East Asian (EAS)

AF:

0.266

AC:

1374

AN:

5162

South Asian (SAS)

AF:

0.216

AC:

1042

AN:

4818

European-Finnish (FIN)

AF:

0.125

AC:

1319

AN:

10592

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21577

AN:

67980

Other (OTH)

AF:

0.361

AC:

764

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1679

3359

5038

6718

8397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.340

Hom.:

7972

Bravo

AF:

0.379

Asia WGS

AF:

0.278

AC:

968

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.092

(source)

DANN

Benign

0.57

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over