rs576118

Positions:

• chr11-68410240-G-A
• chr11-68410240-G-C
• chr11-68410240-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002335.4(LRP5):​c.2318+100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 933,354 control chromosomes in the GnomAD database, including 266,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38384 hom., cov: 32)
  • Exomes 𝑓: 0.76 (228526 hom.)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.44

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-68410240-G-A is Benign according to our data. Variant chr11-68410240-G-A is described in ClinVar as [Benign]. Clinvar id is 1269443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	c.2318+100G>A		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.2318+100G>A		intron_variant		1	NM_002335.4	ENSP00000294304.6
LRP5	ENST00000529993.5	n.*924+100G>A		intron_variant		1		ENSP00000436652.1
LRP5	ENST00000528714.1	n.112+100G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106042 AN: 151968 Hom.: 38379 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.752

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: 0.692

GnomAD4 exome AF: 0.762 AC: 595480 AN: 781268 Hom.: 228526 AF XY: 0.767 AC XY: 312908 AN XY: 408172

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.738

Gnomad4 ASJ exome AF: 0.738

Gnomad4 EAS exome AF: 0.736

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.913

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.697 AC: 106078 AN: 152086 Hom.: 38384 Cov.: 32 AF XY: 0.709 AC XY: 52727 AN XY: 74346

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.693

Alfa AF: 0.734 Hom.: 39608

Bravo AF: 0.667

Asia WGS AF: 0.789 AC: 2742 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.91
CADD	Benign	0.10
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

Other links and lift over

dbSNP: rs576118; hg19: chr11-68177708;