rs1800168

Variant names:

• chr12-57198774-C-T
• rs1800168
• NM_002332.3:c.9676+104C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57198774-C-T
• chr12-57198774-C-A
• chr12-57198774-C-G

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.9676+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,158,212 control chromosomes in the GnomAD database, including 256,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (26307 hom., cov: 32)
  • Exomes 𝑓: 0.67 (229884 hom.)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.503
• Publications: 16 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=-0.82).
• BP6: Variant 12-57198774-C-T is Benign according to our data. Variant chr12-57198774-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	NM_002332.3	MANE Select	c.9676+104C>T		intron	N/A	NP_002323.2	Q07954-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	ENST00000243077.8	TSL:1 MANE Select	c.9676+104C>T		intron	N/A	ENSP00000243077.3	Q07954-1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86034 AN: 151946 Hom.: 26307 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.670 AC: 674609 AN: 1006148 Hom.: 229884 AF XY: 0.678 AC XY: 341640 AN XY: 504264

African (AFR) AF: 0.312 AC: 7683 AN: 24610

American (AMR) AF: 0.496 AC: 16804 AN: 33882

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 13943 AN: 20382

East Asian (EAS) AF: 0.595 AC: 20052 AN: 33714

South Asian (SAS) AF: 0.786 AC: 50863 AN: 64750

European-Finnish (FIN) AF: 0.601 AC: 19796 AN: 32946

Middle Eastern (MID) AF: 0.660 AC: 3210 AN: 4862

European-Non Finnish (NFE) AF: 0.688 AC: 512877 AN: 745994

Other (OTH) AF: 0.653 AC: 29381 AN: 45008

GnomAD4 genome AF: 0.566 AC: 86043 AN: 152064 Hom.: 26307 Cov.: 32 AF XY: 0.569 AC XY: 42268 AN XY: 74342

African (AFR) AF: 0.322 AC: 13356 AN: 41466

American (AMR) AF: 0.585 AC: 8941 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2794 AN: 5162

South Asian (SAS) AF: 0.766 AC: 3693 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6419 AN: 10580

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46513 AN: 67962

Other (OTH) AF: 0.596 AC: 1260 AN: 2114

Alfa AF: 0.549 Hom.: 2976

Bravo AF: 0.543

Asia WGS AF: 0.574 AC: 2000 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		-0.50
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: rs1800168; hg19: chr12-57592557; COSMIC: COSV54505324; COSMIC: COSV54505324;