11-68438110-T-C

Position:

• chr11-68438110-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002335.4(LRP5):​c.4112-336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,180 control chromosomes in the GnomAD database, including 9,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9961 hom., cov: 33)
• Consequence: LRP5 NM_002335.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.31

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-68438110-T-C is Benign according to our data. Variant chr11-68438110-T-C is described in ClinVar as [Benign]. Clinvar id is 1295656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP5	NM_002335.4	c.4112-336T>C		intron_variant		ENST00000294304.12	NP_002326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP5	ENST00000294304.12	c.4112-336T>C		intron_variant		1	NM_002335.4	ENSP00000294304	P1
LRP5	ENST00000529993.5	c.*2718-336T>C		intron_variant, NMD_transcript_variant		1		ENSP00000436652

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52444 AN: 152062 Hom.: 9937 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.345 AC: 52513 AN: 152180 Hom.: 9961 Cov.: 33 AF XY: 0.334 AC XY: 24858 AN XY: 74406

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.357

Alfa AF: 0.335 Hom.: 8609

Bravo AF: 0.373

Asia WGS AF: 0.283 AC: 987 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.93
CADD	Benign	0.22
DANN	Benign	0.32

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: rs901823; hg19: chr11-68205578;