11-68414907-T-C

Position:

• chr11-68414907-T-C

Variant summary

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

The NM_002335.4(LRP5):​c.2827+895T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,234 control chromosomes in the GnomAD database, including 1,456 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 0.13 (1456 hom., cov: 33)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.2827+895T>C		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.2827+895T>C		intron_variant		1	NM_002335.4	ENSP00000294304.6
LRP5	ENST00000529993.5	n.*1433+895T>C		intron_variant		1		ENSP00000436652.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19425 AN: 152116 Hom.: 1455 Cov.: 33

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.128 AC: 19441 AN: 152234 Hom.: 1456 Cov.: 33 AF XY: 0.122 AC XY: 9093 AN XY: 74436

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0844

Gnomad4 FIN AF: 0.0433

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.149

Alfa AF: 0.150 Hom.: 2406

Bravo AF: 0.142

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.61

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: rs923346; hg19: chr11-68182375;