rs1800159

chr12-57200111-A-Gchr12-57200111-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.0830

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1265558.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
LRP1	NM_002332.3	c.10014+86A>G		intron_variant		ENST00000243077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1	ENST00000243077.8	c.10014+86A>G		intron_variant		1	NM_002332.3	P1

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

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.693

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.672

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.640

Alfa AF: 0.672 Hom.: 45598

Bravo AF: 0.628

Asia WGS AF: 0.637 AC: 2216 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	13
Dann	Benign	0.90

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: rs1800159; hg19: chr12-57593894;