NM_002332.3:c.8574C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002332.3(LRP1):c.8574C>T(p.Cys2858Cys) 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

Publications

30 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	NM_002332.3	MANE Select	c.8574C>T	p.Cys2858Cys	synonymous	Exon 54 of 89	NP_002323.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	ENST00000243077.8	TSL:1 MANE Select	c.8574C>T	p.Cys2858Cys	synonymous	Exon 54 of 89	ENSP00000243077.3

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

GnomAD2 exomes

AF:

0.357

AC:

89396

AN:

250394

AF XY:

0.338

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 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

African (AFR)

AF:

0.498

AC:

16686

AN:

33480

American (AMR)

AF:

0.503

AC:

22497

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

7933

AN:

26136

East Asian (EAS)

AF:

0.368

AC:

14605

AN:

39698

South Asian (SAS)

AF:

0.212

AC:

18256

AN:

86250

European-Finnish (FIN)

AF:

0.400

AC:

21190

AN:

52972

Middle Eastern (MID)

AF:

0.329

AC:

1896

AN:

5766

European-Non Finnish (NFE)

AF:

0.313

AC:

347931

AN:

1111914

Other (OTH)

AF:

0.326

AC:

19711

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19844

39688

59533

79377

99221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11522

23044

34566

46088

57610

<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:

0.380

AC:

57808

AN:

152030

Hom.:

11613

Cov.:

AF XY:

0.379

AC XY:

28133

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.499

AC:

20655

AN:

41434

American (AMR)

AF:

0.397

AC:

6069

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1077

AN:

3472

East Asian (EAS)

AF:

0.407

AC:

2106

AN:

5170

South Asian (SAS)

AF:

0.230

AC:

1109

AN:

4818

European-Finnish (FIN)

AF:

0.393

AC:

4159

AN:

10574

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21378

AN:

67964

Other (OTH)

AF:

0.365

AC:

767

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1821

3643

5464

7286

9107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.340

Hom.:

4724

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

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Keratosis pilaris

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

2.2

(source)

DANN

Benign

0.82

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over