dbSNP rs2306692: LRP1:c.841+1992C>T (chr12-57147482-C-T) – 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.841+1992C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,144 control chromosomes in the GnomAD database, including 2,860 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 0.18 ( 2857 hom., cov: 32)

Exomes 𝑓: 0.13 ( 3 hom. )

Consequence

LRP1
NM_002332.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

9 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 links:

LRP1-AS (HGNC:51694): (LRP1 antisense RNA)

LRP1-AS links:

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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=-0.71).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LRP1	NM_002332.3 link	c.841+1992C>T	intron_variant	Intron 6 of 88	ENST00000243077.8	NP_002323.2	Q07954-1Q59FG2
LRP1-AS	NR_131938.2 link	n.138G>A	non_coding_transcript_exon_variant	Exon 1 of 2
LRP1-AS	NR_131939.2 link	n.138G>A	non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8 link	c.841+1992C>T		intron_variant	Intron 6 of 88	1	NM_002332.3	ENSP00000243077.3		Q07954-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27671

AN:

151878

Hom.:

2851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.128

AC:

AN:

148

Hom.:

Cov.:

AF XY:

0.102

AC XY:

AN XY:

108

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.111

AC:

AN:

126

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.182

AC:

27707

AN:

151996

Hom.:

2857

Cov.:

AF XY:

0.184

AC XY:

13670

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.245

AC:

10171

AN:

41440

American (AMR)

AF:

0.213

AC:

3254

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

407

AN:

3470

East Asian (EAS)

AF:

0.341

AC:

1758

AN:

5148

South Asian (SAS)

AF:

0.128

AC:

615

AN:

4820

European-Finnish (FIN)

AF:

0.163

AC:

1728

AN:

10600

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9265

AN:

67920

Other (OTH)

AF:

0.189

AC:

399

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1113

2225

3338

4450

5563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.150

Hom.:

2169

Bravo

AF:

0.187

Asia WGS

AF:

0.251

AC:

875

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.1

(source)

DANN

Benign

0.68

PhyloP100

-1.1

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