Genetic Variant LRP1:c.10595-220C>T (chr12-57202201-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002332.3(LRP1):c.10595-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,740 control chromosomes in the GnomAD database, including 11,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 11971 hom., cov: 30)

Consequence

LRP1
NM_002332.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.234

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 12-57202201-C-T is Benign according to our data. Variant chr12-57202201-C-T is described in ClinVar as [Benign]. Clinvar id is 1226272.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1	NM_002332.3 link	c.10595-220C>T		intron_variant	Intron 67 of 88	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.10595-220C>T		intron_variant	Intron 67 of 88	1	NM_002332.3	ENSP00000243077.3		Q07954-1
LRP1	ENST00000555124.1 link	c.338-220C>T		intron_variant	Intron 3 of 4	4		ENSP00000451012.1		H0YJ88

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58673

AN:

151622

Hom.:

11953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.375

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

GnomAD4 genome

AF:

0.387

AC:

58720

AN:

151740

Hom.:

11971

Cov.:

AF XY:

0.384

AC XY:

28453

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.335

Hom.:

4071

Bravo

AF:

0.395

Asia WGS

AF:

0.329

AC:

1142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

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

-0.77

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over