11-68424878-T-G

Position:

• chr11-68424878-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000294304.12(LRP5):​c.3237-224T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,140 control chromosomes in the GnomAD database, including 9,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.34 (9550 hom., cov: 33)
• Consequence: LRP5 ENST00000294304.12 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0210

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-68424878-T-G is Benign according to our data. Variant chr11-68424878-T-G is described in ClinVar as [Benign]. Clinvar id is 1222543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.3237-224T>G		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.3237-224T>G		intron_variant		1	NM_002335.4	ENSP00000294304.6
LRP5	ENST00000529993.5	n.*1843-224T>G		intron_variant		1		ENSP00000436652.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51248 AN: 152020 Hom.: 9531 Cov.: 33

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.337 AC: 51317 AN: 152140 Hom.: 9550 Cov.: 33 AF XY: 0.325 AC XY: 24188 AN XY: 74372

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.350

Alfa AF: 0.318 Hom.: 8114

Bravo AF: 0.366

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.30

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: rs599083; hg19: chr11-68192346;