Variant rs11172124 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002332.3(LRP1):c.10345+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,808 control chromosomes in the GnomAD database, including 47,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.22 ( 3811 hom., cov: 31)

Exomes 𝑓: 0.24 ( 43498 hom. )

Consequence

LRP1
NM_002332.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-57201172-G-A is Benign according to our data. Variant chr12-57201172-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1	NM_002332.3 linkuse as main transcript	c.10345+19G>A		intron_variant		ENST00000243077.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
LRP1	ENST00000243077.8 linkuse as main transcript	c.10345+19G>A	intron_variant	1	NM_002332.3	P1	Q07954-1
LRP1	ENST00000555124.1 linkuse as main transcript	c.46+19G>A	intron_variant	4
LRP1	ENST00000555941.1 linkuse as main transcript		downstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33173

AN:

152002

Hom.:

3810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.225

AC:

56331

AN:

250486

Hom.:

6935

AF XY:

0.218

AC XY:

29474

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.239

AC:

348636

AN:

1460688

Hom.:

43498

Cov.:

AF XY:

0.234

AC XY:

170107

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.249

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.271

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.218

AC:

33188

AN:

152120

Hom.:

3811

Cov.:

AF XY:

0.214

AC XY:

15947

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.191

Hom.:

857

Bravo

AF:

0.220

Asia WGS

AF:

0.140

AC:

489

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.6

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over