chr11-68309770-T-C

Position:

• chr11-68309770-T-C

Variant summary

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

The XM_011545029.2(LRP5):​c.118+10772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 151,990 control chromosomes in the GnomAD database, including 49,685 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 0.81 (49685 hom., cov: 30)
• Consequence: LRP5 XM_011545029.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	XM_011545029.2	c.118+10772T>C		intron_variant			XP_011543331.1
LRP5	XM_011545030.2	c.118+10772T>C		intron_variant			XP_011543332.1
LRP5	XM_011545031.2	c.118+10772T>C		intron_variant			XP_011543333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122556 AN: 151872 Hom.: 49643 Cov.: 30

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.807 AC: 122648 AN: 151990 Hom.: 49685 Cov.: 30 AF XY: 0.804 AC XY: 59689 AN XY: 74284

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.825

Alfa AF: 0.805 Hom.: 46891

Bravo AF: 0.824

Asia WGS AF: 0.773 AC: 2686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs312009; hg19: chr11-68077238;