rs312023

Positions:

• chr11-68329581-G-A
• chr11-68329581-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+16776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,124 control chromosomes in the GnomAD database, including 19,474 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 0.46 (19474 hom., cov: 33)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

LOC124902698 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.91+16776G>A		intron_variant		ENST00000294304.12	NP_002326.2
LOC124902698	XR_007062748.1	n.279-1119C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.91+16776G>A		intron_variant		1	NM_002335.4	ENSP00000294304	P1
LRP5	ENST00000529993.5	c.91+16776G>A		intron_variant, NMD_transcript_variant		1		ENSP00000436652

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69605 AN: 152006 Hom.: 19458 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.458 AC: 69630 AN: 152124 Hom.: 19474 Cov.: 33 AF XY: 0.472 AC XY: 35124 AN XY: 74348

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.484

Alfa AF: 0.486 Hom.: 3066

Bravo AF: 0.433

Asia WGS AF: 0.724 AC: 2515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.77

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: rs312023; hg19: chr11-68097049;