rs3781590

Positions:

• chr11-68391684-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002335.4(LRP5):​c.1584+1632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,176 control chromosomes in the GnomAD database, including 9,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9686 hom., cov: 33)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4	c.1584+1632G>A		intron_variant		ENST00000294304.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP5	ENST00000294304.12	c.1584+1632G>A		intron_variant		1	NM_002335.4	P1
LRP5	ENST00000529993.5	c.1412+4972G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52369 AN: 152058 Hom.: 9664 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.345 AC: 52432 AN: 152176 Hom.: 9686 Cov.: 33 AF XY: 0.333 AC XY: 24780 AN XY: 74400

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.346

Alfa AF: 0.339 Hom.: 14702

Bravo AF: 0.377

Asia WGS AF: 0.146 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.0
DANN	Benign	0.74

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: rs3781590; hg19: chr11-68159152;