Variant 11-68410260-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002335.4(LRP5):c.2318+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 812,530 control chromosomes in the GnomAD database, including 231,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 37547 hom., cov: 32)

Exomes 𝑓: 0.76 ( 193512 hom. )

Consequence

LRP5
NM_002335.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-68410260-C-T is Benign according to our data. Variant chr11-68410260-C-T is described in ClinVar as [Benign]. Clinvar id is 1291233.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 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.2318+120C>T		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
LRP5	ENST00000294304.12 linkuse as main transcript	c.2318+120C>T	intron_variant	1	NM_002335.4	ENSP00000294304	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.*924+120C>T	intron_variant, NMD_transcript_variant	1		ENSP00000436652
LRP5	ENST00000528714.1 linkuse as main transcript	n.112+120C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104415

AN:

151962

Hom.:

37541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.751

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.927

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.679

GnomAD4 exome

AF:

0.762

AC:

503391

AN:

660450

Hom.:

193512

AF XY:

0.768

AC XY:

269194

AN XY:

350588

show subpopulations

Gnomad4 AFR exome

AF:

0.470

Gnomad4 AMR exome

AF:

0.736

Gnomad4 ASJ exome

AF:

0.737

Gnomad4 EAS exome

AF:

0.735

Gnomad4 SAS exome

AF:

0.836

Gnomad4 FIN exome

AF:

0.913

Gnomad4 NFE exome

AF:

0.756

Gnomad4 OTH exome

AF:

0.742

GnomAD4 genome

AF:

0.687

AC:

104449

AN:

152080

Hom.:

37547

Cov.:

AF XY:

0.699

AC XY:

51968

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.716

Gnomad4 ASJ

AF:

0.751

Gnomad4 EAS

AF:

0.782

Gnomad4 SAS

AF:

0.841

Gnomad4 FIN

AF:

0.927

Gnomad4 NFE

AF:

0.757

Gnomad4 OTH

AF:

0.681

Alfa

AF:

0.721

Hom.:

6368

Bravo

AF:

0.655

Asia WGS

AF:

0.788

AC:

2738

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.89

CADD

Benign

0.12

DANN

Benign

0.53

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