rs2508836

chr11-68323797-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+10992C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,170 control chromosomes in the GnomAD database, including 3,919 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 0.21 (3919 hom., cov: 32)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4	c.91+10992C>T		intron_variant		ENST00000294304.12
LOC124900302	XR_007062749.1	n.10349C>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+10992C>T		intron_variant		1	NM_002335.4	P1
LRP5	ENST00000529993.5	c.91+10992C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31340 AN: 152052 Hom.: 3922 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.206 AC: 31326 AN: 152170 Hom.: 3919 Cov.: 32 AF XY: 0.201 AC XY: 14967 AN XY: 74372

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.217

Alfa AF: 0.227 Hom.: 697

Bravo AF: 0.202

Asia WGS AF: 0.0990 AC: 345 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	0.62

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: rs2508836; hg19: chr11-68091265;