Variant rs901824 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 ENST00000294304.12(LRP5):c.4348+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,602,452 control chromosomes in the GnomAD database, including 6,438 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 ( 5557 hom. )

Consequence

LRP5
ENST00000294304.12 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.60

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:

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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=-0.9).

BP6

Variant 11-68438705-T-C is Benign according to our data. Variant chr11-68438705-T-C is described in ClinVar as [Benign]. Clinvar id is 1263486.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+23T>C		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
LRP5	ENST00000294304.12 linkuse as main transcript	c.4348+23T>C	intron_variant	1	NM_002335.4	ENSP00000294304	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.*2954+23T>C	intron_variant, NMD_transcript_variant	1		ENSP00000436652
LRP5	ENST00000533695.1 linkuse as main transcript	n.90+23T>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0982

AC:

14944

AN:

152176

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:

0.0434

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0868

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0749

AC:

18122

AN:

242098

Hom.:

746

AF XY:

0.0740

AC XY:

9770

AN XY:

132064

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.0890

Gnomad EAS exome

AF:

0.0382

Gnomad SAS exome

AF:

0.0384

Gnomad FIN exome

AF:

0.0501

Gnomad NFE exome

AF:

0.0894

Gnomad OTH exome

AF:

0.0813

GnomAD4 exome

AF:

0.0849

AC:

123106

AN:

1450158

Hom.:

5557

Cov.:

AF XY:

0.0835

AC XY:

60256

AN XY:

721952

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.0581

Gnomad4 ASJ exome

AF:

0.0894

Gnomad4 EAS exome

AF:

0.0455

Gnomad4 SAS exome

AF:

0.0395

Gnomad4 FIN exome

AF:

0.0490

Gnomad4 NFE exome

AF:

0.0897

Gnomad4 OTH exome

AF:

0.0913

GnomAD4 genome

AF:

0.0982

AC:

14956

AN:

152294

Hom.:

881

Cov.:

AF XY:

0.0949

AC XY:

7068

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.0742

Gnomad4 ASJ

AF:

0.0919

Gnomad4 EAS

AF:

0.0433

Gnomad4 SAS

AF:

0.0449

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0868

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0901

Hom.:

317

Bravo

AF:

0.105

Asia WGS

AF:

0.0750

AC:

263

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

DANN

Benign

0.37

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