Variant 11-68312746-C-CGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002335.4(LRP5):c.58_60dup(p.Leu20dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,060,778 control chromosomes in the GnomAD database, including 2,064 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 821 hom., cov: 28)

Exomes 𝑓: 0.080 ( 1243 hom. )

Consequence

LRP5
NM_002335.4 inframe_insertion

Scores

Not classified

Clinical Significance

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 -16 ACMG points.

BP6

Variant 11-68312746-C-CGCT is Benign according to our data. Variant chr11-68312746-C-CGCT is described in ClinVar as [Benign]. Clinvar id is 193231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4 linkuse as main transcript	c.58_60dup	p.Leu20dup	inframe_insertion	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_60dup	p.Leu20dup	inframe_insertion	1/23	1	NM_002335.4	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.58_60dup	p.Leu20dup	inframe_insertion, NMD_transcript_variant	1/23	1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

14633

AN:

144284

Hom.:

819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.0125

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.0729

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.0839

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.0724

AC:

1181

AN:

16308

Hom.:

AF XY:

0.0727

AC XY:

717

AN XY:

9856

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.0152

Gnomad SAS exome

AF:

0.0604

Gnomad FIN exome

AF:

0.0984

Gnomad NFE exome

AF:

0.0752

Gnomad OTH exome

AF:

0.0913

GnomAD4 exome

AF:

0.0805

AC:

73751

AN:

916408

Hom.:

1243

Cov.:

AF XY:

0.0807

AC XY:

35351

AN XY:

438204

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.0528

Gnomad4 ASJ exome

AF:

0.0949

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.0660

Gnomad4 FIN exome

AF:

0.0957

Gnomad4 NFE exome

AF:

0.0796

Gnomad4 OTH exome

AF:

0.0811

GnomAD4 genome

AF:

0.101

AC:

14647

AN:

144370

Hom.:

821

Cov.:

AF XY:

0.101

AC XY:

7085

AN XY:

70296

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0695

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.0177

Gnomad4 SAS

AF:

0.0733

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.0839

Gnomad4 OTH

AF:

0.0863

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Mar 06, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 12, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2015	- -

Exudative vitreoretinopathy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

African/African American population allele frequency is 13.45% (rs564221347, 1220/7934 alleles, 89 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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