chr12-57191361-C-T

Variant names:

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.7278C>T(p.Ala2426Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,611,140 control chromosomes in the GnomAD database, including 358,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 26299 hom., cov: 32)

Exomes 𝑓: 0.67 ( 332152 hom. )

Consequence

LRP1
NM_002332.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.92

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=-0.59).

BP6

Variant 12-57191361-C-T is Benign according to our data. Variant chr12-57191361-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1	NM_002332.3 link	c.7278C>T	p.Ala2426Ala	synonymous_variant	Exon 44 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.7278C>T	p.Ala2426Ala	synonymous_variant	Exon 44 of 89	1	NM_002332.3	ENSP00000243077.3		Q07954-1
LRP1	ENST00000554118.1 link	c.291+352C>T		intron_variant	Intron 2 of 2	2		ENSP00000451622.1		H0YJI8

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86012

AN:

151802

Hom.:

26299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.593

GnomAD2 exomes

AF:

0.623

AC:

155855

AN:

250068

AF XY:

0.646

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.548

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.670

AC:

977287

AN:

1459220

Hom.:

332152

Cov.:

AF XY:

0.676

AC XY:

490628

AN XY:

725454

show subpopulations

African (AFR)

AF:

0.313

AC:

10455

AN:

33422

American (AMR)

AF:

0.485

AC:

21646

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

17816

AN:

26066

East Asian (EAS)

AF:

0.588

AC:

23278

AN:

39622

South Asian (SAS)

AF:

0.785

AC:

67689

AN:

86192

European-Finnish (FIN)

AF:

0.600

AC:

32017

AN:

53358

Middle Eastern (MID)

AF:

0.657

AC:

3783

AN:

5760

European-Non Finnish (NFE)

AF:

0.686

AC:

761132

AN:

1109964

Other (OTH)

AF:

0.655

AC:

39471

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

17400

34799

52199

69598

86998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19354

38708

58062

77416

96770

<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:

0.566

AC:

86023

AN:

151920

Hom.:

26299

Cov.:

AF XY:

0.569

AC XY:

42233

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.325

AC:

13458

AN:

41376

American (AMR)

AF:

0.583

AC:

8910

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

2353

AN:

3472

East Asian (EAS)

AF:

0.540

AC:

2786

AN:

5160

South Asian (SAS)

AF:

0.764

AC:

3689

AN:

4826

European-Finnish (FIN)

AF:

0.605

AC:

6399

AN:

10574

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.684

AC:

46457

AN:

67922

Other (OTH)

AF:

0.595

AC:

1256

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1772

3543

5315

7086

8858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<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:

0.641

Hom.:

86352

Bravo

AF:

0.543

Asia WGS

AF:

0.570

AC:

1985

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.691

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 02, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.13

(source)

DANN

Benign

0.89

PhyloP100

-4.9

Mutation Taster

=89/11

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