dbSNP rs4759044: LRP1:c.68-1572T>C (chr12-57136887-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002332.3(LRP1):c.68-1572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,992 control chromosomes in the GnomAD database, including 15,069 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15069 hom., cov: 32)

Consequence

LRP1
NM_002332.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Publications

14 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1	NM_002332.3 link	c.68-1572T>C		intron_variant	Intron 1 of 88	ENST00000243077.8	NP_002323.2	Q07954-1Q59FG2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP1	ENST00000243077.8 link	c.68-1572T>C	intron_variant	Intron 1 of 88	1	NM_002332.3	ENSP00000243077.3	Q07954-1
LRP1	ENST00000554174.1 link	c.68-1572T>C	intron_variant	Intron 1 of 7	1		ENSP00000451737.1	Q6PJ72
LRP1	ENST00000553277.5 link	c.68-1572T>C	intron_variant	Intron 1 of 6	1		ENSP00000451449.1	Q7Z7K9
LRP1	ENST00000338962.8 link	c.68-1572T>C	intron_variant	Intron 1 of 6	1		ENSP00000341264.4	Q07954-2

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

67003

AN:

151876

Hom.:

15052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.441

AC:

67064

AN:

151992

Hom.:

15069

Cov.:

AF XY:

0.439

AC XY:

32604

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.449

AC:

18600

AN:

41400

American (AMR)

AF:

0.538

AC:

8225

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1405

AN:

3472

East Asian (EAS)

AF:

0.248

AC:

1283

AN:

5180

South Asian (SAS)

AF:

0.390

AC:

1876

AN:

4816

European-Finnish (FIN)

AF:

0.416

AC:

4396

AN:

10568

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.440

AC:

29899

AN:

67958

Other (OTH)

AF:

0.430

AC:

909

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1918

3836

5755

7673

9591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.443

Hom.:

12018

Bravo

AF:

0.451

Asia WGS

AF:

0.364

AC:

1267

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.9

(source)

DANN

Benign

0.51

PhyloP100

-0.021

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over