11-68365263-A-G

Position:

• chr11-68365263-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002335.4(LRP5):​c.884-308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 106,578 control chromosomes in the GnomAD database, including 19,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (19492 hom., cov: 29)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-68365263-A-G is Benign according to our data. Variant chr11-68365263-A-G is described in ClinVar as [Benign]. Clinvar id is 1262200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.884-308A>G		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.884-308A>G		intron_variant		1	NM_002335.4	ENSP00000294304.6
LRP5	ENST00000529993.5	n.884-308A>G		intron_variant		1		ENSP00000436652.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 72130 AN: 106476 Hom.: 19445 Cov.: 29

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.650

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.678 AC: 72226 AN: 106578 Hom.: 19492 Cov.: 29 AF XY: 0.676 AC XY: 34403 AN XY: 50876

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.650

Alfa AF: 0.430 Hom.: 1806

Bravo AF: 0.513

Asia WGS AF: 0.205 AC: 704 AN: 3410

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs314775; hg19: chr11-68132731;