11-68317494-G-C

Position:

• chr11-68317494-G-C

Variant summary

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

The NM_002335.4(LRP5):​c.91+4689G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,930 control chromosomes in the GnomAD database, including 14,111 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 0.42 (14111 hom., cov: 31)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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]

LOC124900302 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.91+4689G>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.91+4689G>C		intron_variant		1	NM_002335.4	ENSP00000294304.6
LRP5	ENST00000529993.5	n.91+4689G>C		intron_variant		1		ENSP00000436652.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64429 AN: 151812 Hom.: 14099 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.424 AC: 64477 AN: 151930 Hom.: 14111 Cov.: 31 AF XY: 0.430 AC XY: 31947 AN XY: 74262

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.443

Alfa AF: 0.256 Hom.: 583

Bravo AF: 0.432

Asia WGS AF: 0.562 AC: 1952 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	3.4
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs312014; hg19: chr11-68084962;