Variant 11-68312746-CGCTGCTGCTGCTGCT-CGCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1

The NM_002335.4(LRP5):c.58_60del(p.Leu20del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 951,934 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0083 ( 1 hom. )

Consequence

LRP5
NM_002335.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00

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 -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-68312746-CGCT-C is Benign according to our data. Variant chr11-68312746-CGCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 193232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68312746-CGCT-C is described in Lovd as [Likely_benign]. Variant chr11-68312746-CGCT-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00826 (6669/807536) while in subpopulation AMR AF= 0.0365 (219/6000). AF 95% confidence interval is 0.0325. There are 1 homozygotes in gnomad4_exome. There are 3666 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4 linkuse as main transcript	c.58_60del	p.Leu20del	inframe_deletion	1/23	ENST00000294304.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP5	ENST00000294304.12 linkuse as main transcript	c.58_60del	p.Leu20del	inframe_deletion	1/23	1	NM_002335.4	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.58_60del	p.Leu20del	inframe_deletion, NMD_transcript_variant	1/23	1

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

144312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000820

Gnomad ASJ

AF:

0.00119

Gnomad EAS

AF:

0.00324

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000479

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000522

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0588

AC:

959

AN:

16308

Hom.:

AF XY:

0.0602

AC XY:

593

AN XY:

9856

show subpopulations

Gnomad AFR exome

AF:

0.0367

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0604

Gnomad EAS exome

AF:

0.0985

Gnomad SAS exome

AF:

0.0629

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.0600

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.00826

AC:

6669

AN:

807536

Hom.:

AF XY:

0.00948

AC XY:

3666

AN XY:

386868

show subpopulations

Gnomad4 AFR exome

AF:

0.00592

Gnomad4 AMR exome

AF:

0.0365

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.0196

Gnomad4 SAS exome

AF:

0.0254

Gnomad4 FIN exome

AF:

0.0433

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00892

GnomAD4 genome

AF:

0.000630

AC:

AN:

144398

Hom.:

Cov.:

AF XY:

0.000654

AC XY:

AN XY:

70302

show subpopulations

Gnomad4 AFR

AF:

0.000550

Gnomad4 AMR

AF:

0.000819

Gnomad4 ASJ

AF:

0.00119

Gnomad4 EAS

AF:

0.00305

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000479

Gnomad4 NFE

AF:

0.000522

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 19, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 12, 2016	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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