chr12-57141483-C-T

Position:

chr12-57141483-C-T

Variant summary

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

The NM_002332.3(LRP1):c.300C>T(p.Asp100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,992 control chromosomes in the GnomAD database, including 17,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1265 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15953 hom. )

Consequence

LRP1
NM_002332.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: -2.02

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=-0.35).

BP6

Variant 12-57141483-C-T is Benign according to our data. Variant chr12-57141483-C-T is described in ClinVar as [Benign]. Clinvar id is 930178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57141483-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.300C>T	p.Asp100=	synonymous_variant	3/89	ENST00000243077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1	ENST00000243077.8 linkuse as main transcript	c.300C>T	p.Asp100=	synonymous_variant	3/89	1	NM_002332.3	P1	Q07954-1
LRP1	ENST00000554174.1 linkuse as main transcript	c.300C>T	p.Asp100=	synonymous_variant	3/8	1
LRP1	ENST00000553277.5 linkuse as main transcript	c.300C>T	p.Asp100=	synonymous_variant	3/7	1
LRP1	ENST00000338962.8 linkuse as main transcript	c.300C>T	p.Asp100=	synonymous_variant	3/7	1			Q07954-2

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18129

AN:

152128

Hom.:

1262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0866

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0668

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.129

AC:

32334

AN:

251146

Hom.:

2503

AF XY:

0.134

AC XY:

18155

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0525

Gnomad AMR exome

AF:

0.0653

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.0555

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.144

AC:

210412

AN:

1461746

Hom.:

15953

Cov.:

AF XY:

0.145

AC XY:

105732

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0531

Gnomad4 AMR exome

AF:

0.0677

Gnomad4 ASJ exome

AF:

0.220

Gnomad4 EAS exome

AF:

0.0821

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.119

AC:

18129

AN:

152246

Hom.:

1265

Cov.:

AF XY:

0.123

AC XY:

9132

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.0865

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.0670

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.143

Hom.:

2677

Bravo

AF:

0.107

Asia WGS

AF:

0.0970

AC:

337

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.153

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:4

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	This variant is associated with the following publications: (PMID: 22819221, 12732394, 28924541, 11076057, 9633759) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Keratosis pilaris

Pathogenic:1

Likely pathogenic, no assertion criteria provided

case-control

Endocrine Laboratory of Southeast University, Southeast University

Jan 01, 2019

early diagnosis and prevention on AD -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

LRP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 07, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.1

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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