Variant rs1140648 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002332.3(LRP1):c.9783G>A(p.Thr3261=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,613,320 control chromosomes in the GnomAD database, including 355,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25991 hom., cov: 34)

Exomes 𝑓: 0.67 ( 329878 hom. )

Consequence

LRP1
NM_002332.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -8.57

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-57199318-G-A is Benign according to our data. Variant chr12-57199318-G-A is described in ClinVar as [Benign]. Clinvar id is 1300111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57199318-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-8.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 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.9783G>A	p.Thr3261=	synonymous_variant	61/89	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.9783G>A	p.Thr3261=	synonymous_variant	61/89	1	NM_002332.3	ENSP00000243077	P1	Q07954-1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85465

AN:

152040

Hom.:

25990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.591

GnomAD3 exomes

AF:

0.621

AC:

155745

AN:

250866

Hom.:

50527

AF XY:

0.644

AC XY:

87364

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.548

Gnomad SAS exome

AF:

0.786

Gnomad FIN exome

AF:

0.595

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.667

AC:

974371

AN:

1461162

Hom.:

329878

Cov.:

AF XY:

0.674

AC XY:

489665

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.482

Gnomad4 ASJ exome

AF:

0.683

Gnomad4 EAS exome

AF:

0.587

Gnomad4 SAS exome

AF:

0.785

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.562

AC:

85474

AN:

152158

Hom.:

25991

Cov.:

AF XY:

0.564

AC XY:

41959

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.316

Gnomad4 AMR

AF:

0.579

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.766

Gnomad4 FIN

AF:

0.607

Gnomad4 NFE

AF:

0.680

Gnomad4 OTH

AF:

0.593

Alfa

AF:

0.641

Hom.:

39484

Bravo

AF:

0.538

Asia WGS

AF:

0.571

AC:

1989

AN:

3478

EpiCase

AF:

0.690

EpiControl

AF:

0.687

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Keratosis pilaris

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.043

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

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