rs11172113

Variant names:

• chr12-57133500-T-C
• rs11172113
• NM_002332.3:c.67+4469T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-57133500-T-C
• chr12-57133500-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002332.3(LRP1):​c.67+4469T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,838 control chromosomes in the GnomAD database, including 13,298 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 0.42 (13298 hom., cov: 30)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 175 publications found

Genes affected

LRP1 (HGNC:6692): (LDL receptor related protein 1) This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015]

LRP1 Gene-Disease associations (from GenCC):

• keratosis follicularis spinulosa decalvans

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• atrophoderma vermiculata

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• developmental dysplasia of the hip 3

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• keratosis pilaris atrophicans

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	NM_002332.3	MANE Select	c.67+4469T>C		intron	N/A	NP_002323.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	ENST00000243077.8	TSL:1 MANE Select	c.67+4469T>C		intron	N/A	ENSP00000243077.3
	LRP1	ENST00000554174.1	TSL:1	c.67+4469T>C		intron	N/A	ENSP00000451737.1
	LRP1	ENST00000553277.5	TSL:1	c.67+4469T>C		intron	N/A	ENSP00000451449.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63012 AN: 151718 Hom.: 13274 Cov.: 30

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.415 AC: 63079 AN: 151838 Hom.: 13298 Cov.: 30 AF XY: 0.417 AC XY: 30947 AN XY: 74230

African (AFR) AF: 0.436 AC: 18026 AN: 41372

American (AMR) AF: 0.513 AC: 7840 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5160

South Asian (SAS) AF: 0.390 AC: 1872 AN: 4802

European-Finnish (FIN) AF: 0.400 AC: 4221 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27236 AN: 67900

Other (OTH) AF: 0.392 AC: 826 AN: 2108

Alfa AF: 0.402 Hom.: 54990

Bravo AF: 0.423

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11172113; hg19: chr12-57527283;