rs4988327

Variant names:

• chr11-68310198-A-G
• rs4988327
• XM_011545029.2:c.118+11200A>G

Variant summary

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

The XM_011545029.2(LRP5):​c.118+11200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 152,226 control chromosomes in the GnomAD database, including 287 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 0.056 (287 hom., cov: 31)
• Consequence: LRP5 XM_011545029.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP5	XM_011545029.2	c.118+11200A>G		intron_variant	Intron 1 of 23		XP_011543331.1
LRP5	XM_011545030.2	c.118+11200A>G		intron_variant	Intron 1 of 22		XP_011543332.1
LRP5	XM_011545031.2	c.118+11200A>G		intron_variant	Intron 1 of 23		XP_011543333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8550 AN: 152108 Hom.: 287 Cov.: 31

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0771

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

GnomAD4 genome AF: 0.0562 AC: 8558 AN: 152226 Hom.: 287 Cov.: 31 AF XY: 0.0546 AC XY: 4060 AN XY: 74418

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0806

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0679 Hom.: 68

Bravo AF: 0.0583

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4988327; hg19: chr11-68077666;