Variant rs901825 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002335.4(LRP5):c.4348+47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,568,886 control chromosomes in the GnomAD database, including 6,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 881 hom., cov: 33)

Exomes 𝑓: 0.085 ( 5384 hom. )

Consequence

LRP5
NM_002335.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.219

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:

LRP5 (HGNC:):

LRP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-68438729-G-C is Benign according to our data. Variant chr11-68438729-G-C is described in ClinVar as [Benign]. Clinvar id is 1223965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4 linkuse as main transcript	c.4348+47G>C		intron_variant		ENST00000294304.12	NP_002326.2	O75197

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LRP5	ENST00000294304.12 linkuse as main transcript	c.4348+47G>C	intron_variant	1	NM_002335.4	ENSP00000294304.6	O75197
LRP5	ENST00000529993.5 linkuse as main transcript	n.*2954+47G>C	intron_variant	1		ENSP00000436652.1	E9PHY1
LRP5	ENST00000533695.1 linkuse as main transcript	n.90+47G>C	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0981

AC:

14931

AN:

152160

Hom.:

880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.0744

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.0432

Gnomad SAS

AF:

0.0445

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0740

AC:

17342

AN:

234232

Hom.:

697

AF XY:

0.0732

AC XY:

9410

AN XY:

128518

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.0880

Gnomad EAS exome

AF:

0.0382

Gnomad SAS exome

AF:

0.0378

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0881

Gnomad OTH exome

AF:

0.0812

GnomAD4 exome

AF:

0.0845

AC:

119773

AN:

1416608

Hom.:

5384

Cov.:

AF XY:

0.0831

AC XY:

58727

AN XY:

706888

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.0578

Gnomad4 ASJ exome

AF:

0.0889

Gnomad4 EAS exome

AF:

0.0456

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0486

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0910

GnomAD4 genome

AF:

0.0981

AC:

14943

AN:

152278

Hom.:

881

Cov.:

AF XY:

0.0948

AC XY:

7058

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.0742

Gnomad4 ASJ

AF:

0.0919

Gnomad4 EAS

AF:

0.0432

Gnomad4 SAS

AF:

0.0447

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0868

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0893

Hom.:

134

Bravo

AF:

0.105

Asia WGS

AF:

0.0750

AC:

262

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

DANN

Benign

0.35

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