Variant chr11-68446651-C-T 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.4586+118C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 907,300 control chromosomes in the GnomAD database, including 4,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 613 hom., cov: 32)

Exomes 𝑓: 0.093 ( 3612 hom. )

Consequence

LRP5
NM_002335.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.94

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:

Genome browser will be placed here

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 11-68446651-C-T is Benign according to our data. Variant chr11-68446651-C-T is described in ClinVar as [Benign]. Clinvar id is 1175466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 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.4586+118C>T		intron_variant		ENST00000294304.12

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
LRP5	ENST00000294304.12 linkuse as main transcript	c.4586+118C>T	intron_variant	1	NM_002335.4	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.*3192+118C>T	intron_variant, NMD_transcript_variant	1
LRP5	ENST00000529702.1 linkuse as main transcript	c.256+118C>T	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12724

AN:

152078

Hom.:

613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0493

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.0814

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0199

Gnomad SAS

AF:

0.0462

Gnomad FIN

AF:

0.0871

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.108

GnomAD4 exome

AF:

0.0932

AC:

70382

AN:

755104

Hom.:

3612

AF XY:

0.0915

AC XY:

36291

AN XY:

396720

show subpopulations

Gnomad4 AFR exome

AF:

0.0505

Gnomad4 AMR exome

AF:

0.0693

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.0285

Gnomad4 SAS exome

AF:

0.0449

Gnomad4 FIN exome

AF:

0.0879

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.0992

GnomAD4 genome

AF:

0.0836

AC:

12725

AN:

152196

Hom.:

613

Cov.:

AF XY:

0.0814

AC XY:

6057

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.0813

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0200

Gnomad4 SAS

AF:

0.0460

Gnomad4 FIN

AF:

0.0871

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0935

Hom.:

Bravo

AF:

0.0840

Asia WGS

AF:

0.0500

AC:

175

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

1.7

DANN

Benign

0.66

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