rs1800159

Variant names:

• chr12-57200111-A-G
• rs1800159
• NM_002332.3:c.10014+86A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57200111-A-G
• chr12-57200111-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002332.3(LRP1):​c.10014+86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,200,058 control chromosomes in the GnomAD database, including 276,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (31921 hom., cov: 27)
  • Exomes 𝑓: 0.68 (244406 hom.)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 12-57200111-A-G is Benign according to our data. Variant chr12-57200111-A-G is described in ClinVar as Benign. ClinVar VariationId is 1265558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1	NM_002332.3	c.10014+86A>G		intron_variant	Intron 62 of 88	ENST00000243077.8	NP_002323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8	c.10014+86A>G		intron_variant	Intron 62 of 88	1	NM_002332.3	ENSP00000243077.3
LRP1	ENST00000555941.1	n.-163A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.647 AC: 97623 AN: 150906 Hom.: 31897 Cov.: 27

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.680 AC: 713530 AN: 1049036 Hom.: 244406 Cov.: 13 AF XY: 0.686 AC XY: 361445 AN XY: 527036

African (AFR) AF: 0.629 AC: 14738 AN: 23430

American (AMR) AF: 0.449 AC: 11361 AN: 25280

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 13247 AN: 19118

East Asian (EAS) AF: 0.558 AC: 19928 AN: 35736

South Asian (SAS) AF: 0.819 AC: 53191 AN: 64944

European-Finnish (FIN) AF: 0.638 AC: 31103 AN: 48764

Middle Eastern (MID) AF: 0.693 AC: 2442 AN: 3526

European-Non Finnish (NFE) AF: 0.686 AC: 536838 AN: 782586

Other (OTH) AF: 0.672 AC: 30682 AN: 45652

GnomAD4 genome AF: 0.647 AC: 97692 AN: 151022 Hom.: 31921 Cov.: 27 AF XY: 0.646 AC XY: 47647 AN XY: 73754

African (AFR) AF: 0.624 AC: 25631 AN: 41070

American (AMR) AF: 0.550 AC: 8347 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2388 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2598 AN: 5070

South Asian (SAS) AF: 0.805 AC: 3848 AN: 4780

European-Finnish (FIN) AF: 0.644 AC: 6740 AN: 10460

Middle Eastern (MID) AF: 0.669 AC: 194 AN: 290

European-Non Finnish (NFE) AF: 0.680 AC: 46037 AN: 67698

Other (OTH) AF: 0.640 AC: 1340 AN: 2094

Alfa AF: 0.669 Hom.: 62953

Bravo AF: 0.628

Asia WGS AF: 0.637 AC: 2216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.083
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: rs1800159; hg19: chr12-57593894; COSMIC: COSV99675163; COSMIC: COSV99675163;