11-68418032-C-T

Position:

• chr11-68418032-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.3027+1505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,120 control chromosomes in the GnomAD database, including 38,413 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 0.70 (38413 hom., cov: 32)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.3027+1505C>T		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.3027+1505C>T		intron_variant		1	NM_002335.4	ENSP00000294304	P1
LRP5	ENST00000529993.5	c.*1633+1505C>T		intron_variant, NMD_transcript_variant		1		ENSP00000436652

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106119 AN: 152002 Hom.: 38408 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.698 AC: 106156 AN: 152120 Hom.: 38413 Cov.: 32 AF XY: 0.709 AC XY: 52769 AN XY: 74378

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.693

Alfa AF: 0.734 Hom.: 27035

Bravo AF: 0.667

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.97
DANN	Benign	0.69

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: rs1784235; hg19: chr11-68185500;