11-68379193-T-C

Position:

• chr11-68379193-T-C

Variant summary

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

The NM_002335.4(LRP5):​c.1016-7123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,238 control chromosomes in the GnomAD database, including 2,355 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 0.17 (2355 hom., cov: 32)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4	c.1016-7123T>C		intron_variant		ENST00000294304.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP5	ENST00000294304.12	c.1016-7123T>C		intron_variant		1	NM_002335.4	P1
LRP5	ENST00000529993.5	c.1016-7123T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26384 AN: 152120 Hom.: 2350 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.174 AC: 26415 AN: 152238 Hom.: 2355 Cov.: 32 AF XY: 0.166 AC XY: 12346 AN XY: 74436

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.170

Alfa AF: 0.183 Hom.: 4298

Bravo AF: 0.183

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11826287; hg19: chr11-68146661;