rs1140648

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002332.3(LRP1):c.9783G>A(p.Thr3261Thr) 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

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

keratosis follicularis spinulosa decalvans
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atrophoderma vermiculata
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
developmental dysplasia of the hip 3
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
keratosis pilaris atrophicans
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LRP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1300111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
LRP1	NM_002332.3 link	c.9783G>A	p.Thr3261Thr	synonymous_variant	Exon 61 of 89	ENST00000243077.8	NP_002323.2	Q07954-1Q59FG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8 link	c.9783G>A	p.Thr3261Thr	synonymous_variant	Exon 61 of 89	1	NM_002332.3	ENSP00000243077.3		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

GnomAD2 exomes

AF:

0.621

AC:

155745

AN:

250866

AF XY:

0.644

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 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

African (AFR)

AF:

0.303

AC:

10142

AN:

33480

American (AMR)

AF:

0.482

AC:

21569

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

17848

AN:

26132

East Asian (EAS)

AF:

0.587

AC:

23285

AN:

39696

South Asian (SAS)

AF:

0.785

AC:

67707

AN:

86250

European-Finnish (FIN)

AF:

0.600

AC:

31746

AN:

52908

Middle Eastern (MID)

AF:

0.657

AC:

3787

AN:

5764

European-Non Finnish (NFE)

AF:

0.683

AC:

758938

AN:

1111838

Other (OTH)

AF:

0.652

AC:

39349

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

18342

36684

55027

73369

91711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19308

38616

57924

77232

96540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.562

AC:

85474

AN:

152158

Hom.:

25991

Cov.:

AF XY:

0.564

AC XY:

41959

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.316

AC:

13131

AN:

41504

American (AMR)

AF:

0.579

AC:

8855

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

2349

AN:

3468

East Asian (EAS)

AF:

0.542

AC:

2795

AN:

5158

South Asian (SAS)

AF:

0.766

AC:

3696

AN:

4826

European-Finnish (FIN)

AF:

0.607

AC:

6427

AN:

10596

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.680

AC:

46260

AN:

67994

Other (OTH)

AF:

0.593

AC:

1251

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1798

3596

5394

7192

8990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.629

Hom.:

47873

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

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.043

(source)

DANN

Benign

0.90

PhyloP100

-8.6

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over