Variant 12-57184505-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002332.3(LRP1):c.6186+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,607,578 control chromosomes in the GnomAD database, including 88,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11135 hom., cov: 32)

Exomes 𝑓: 0.32 ( 77775 hom. )

Consequence

LRP1
NM_002332.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0170

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-57184505-C-T is Benign according to our data. Variant chr12-57184505-C-T is described in ClinVar as [Benign]. Clinvar id is 1230367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1	NM_002332.3 linkuse as main transcript	c.6186+53C>T		intron_variant		ENST00000243077.8	NP_002323.2	Q07954-1Q59FG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8 linkuse as main transcript	c.6186+53C>T		intron_variant		1	NM_002332.3	ENSP00000243077.3		Q07954-1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56797

AN:

151976

Hom.:

11119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.406

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.321

AC:

467728

AN:

1455484

Hom.:

77775

AF XY:

0.316

AC XY:

228394

AN XY:

723694

show subpopulations

Gnomad4 AFR exome

AF:

0.476

Gnomad4 AMR exome

AF:

0.502

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.374

AC:

56846

AN:

152094

Hom.:

11135

Cov.:

AF XY:

0.372

AC XY:

27677

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.476

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.404

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.336

Hom.:

1767

Bravo

AF:

0.389

Asia WGS

AF:

0.377

AC:

1309

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.86

CADD

Benign

4.9

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over