Variant 11-68312693-GC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_002335.4(LRP5):c.-19del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00852 in 993,782 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0067 ( 5 hom., cov: 30)

Exomes 𝑓: 0.0088 ( 40 hom. )

Consequence

LRP5
NM_002335.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.493

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 Likely_benign. Variant got -5 ACMG points.

BP6

Variant 11-68312693-GC-G is Benign according to our data. Variant chr11-68312693-GC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287479.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4 linkuse as main transcript	c.-19del		5_prime_UTR_variant	1/23	ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12 linkuse as main transcript	c.-19del		5_prime_UTR_variant	1/23	1	NM_002335.4	ENSP00000294304	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.-19del		5_prime_UTR_variant, NMD_transcript_variant	1/23	1		ENSP00000436652

Frequencies

GnomAD3 genomes

AF:

0.00668

AC:

966

AN:

144672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00225

Gnomad AMR

AF:

0.00492

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00168

Gnomad FIN

AF:

0.00430

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.00502

GnomAD3 exomes

AF:

0.00220

AC:

AN:

908

Hom.:

AF XY:

0.00187

AC XY:

AN XY:

534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00524

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00883

AC:

7498

AN:

848994

Hom.:

Cov.:

AF XY:

0.00867

AC XY:

3447

AN XY:

397760

show subpopulations

Gnomad4 AFR exome

AF:

0.000817

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.000214

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.00648

Gnomad4 NFE exome

AF:

0.00928

Gnomad4 OTH exome

AF:

0.00698

GnomAD4 genome

AF:

0.00667

AC:

966

AN:

144788

Hom.:

Cov.:

AF XY:

0.00591

AC XY:

417

AN XY:

70508

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.0180

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00168

Gnomad4 FIN

AF:

0.00430

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.00496

Alfa

AF:

0.00956

Hom.:

Bravo

AF:

0.00594

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 03, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	LRP5: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 19, 2019	See Variant Classification Assertion Criteria. -

not specified

Benign:1

Likely benign, flagged submission

clinical testing

GeneDx

Aug 17, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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