11-68339796-C-G

Position:

• chr11-68339796-C-G

Variant summary

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

The NM_002335.4(LRP5):​c.92-8051C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,124 control chromosomes in the GnomAD database, including 3,264 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 0.18 (3264 hom., cov: 32)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4	c.92-8051C>G		intron_variant		ENST00000294304.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP5	ENST00000294304.12	c.92-8051C>G		intron_variant		1	NM_002335.4	P1
LRP5	ENST00000529993.5	c.92-8051C>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28020 AN: 152006 Hom.: 3266 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0809

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.184 AC: 28020 AN: 152124 Hom.: 3264 Cov.: 32 AF XY: 0.177 AC XY: 13171 AN XY: 74370

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0807

Gnomad4 SAS AF: 0.0884

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.188

Alfa AF: 0.108 Hom.: 189

Bravo AF: 0.183

Asia WGS AF: 0.0870 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.035
DANN	Benign	0.68

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: rs312777; hg19: chr11-68107264;