rs4988330

Positions:

• chr11-68313531-C-T

Variant summary

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

The NM_002335.4(LRP5):​c.91+726C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 152,274 control chromosomes in the GnomAD database, including 282 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 0.054 (282 hom., cov: 32)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4	c.91+726C>T		intron_variant		ENST00000294304.12
LOC124900302	XR_007062749.1	n.83C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP5	ENST00000294304.12	c.91+726C>T		intron_variant		1	NM_002335.4	P1
LRP5	ENST00000529993.5	c.91+726C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8255 AN: 152156 Hom.: 283 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0542 AC: 8251 AN: 152274 Hom.: 282 Cov.: 32 AF XY: 0.0525 AC XY: 3910 AN XY: 74452

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0806

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0628 Hom.: 41

Bravo AF: 0.0561

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	17
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4988330; hg19: chr11-68080999;