Variant rs1800154 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002332.3(LRP1):c.8574C>T(p.Cys2858=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,613,318 control chromosomes in the GnomAD database, including 90,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11613 hom., cov: 33)

Exomes 𝑓: 0.32 ( 78705 hom. )

Consequence

LRP1
NM_002332.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.69

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 12-57195876-C-T is Benign according to our data. Variant chr12-57195876-C-T is described in ClinVar as [Benign]. Clinvar id is 1222429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 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.8574C>T	p.Cys2858=	synonymous_variant	54/89	ENST00000243077.8	NP_002323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8 linkuse as main transcript	c.8574C>T	p.Cys2858=	synonymous_variant	54/89	1	NM_002332.3	ENSP00000243077	P1	Q07954-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57754

AN:

151914

Hom.:

11596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.357

AC:

89396

AN:

250394

Hom.:

17262

AF XY:

0.338

AC XY:

45782

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.515

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.397

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.322

AC:

470705

AN:

1461288

Hom.:

78705

Cov.:

AF XY:

0.316

AC XY:

229859

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.503

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.368

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.380

AC:

57808

AN:

152030

Hom.:

11613

Cov.:

AF XY:

0.379

AC XY:

28133

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.338

Hom.:

4618

Bravo

AF:

0.397

Asia WGS

AF:

0.374

AC:

1301

AN:

3478

EpiCase

AF:

0.304

EpiControl

AF:

0.308

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Keratosis pilaris

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

2.2

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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