Variant 12-57176231-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_002332.3(LRP1):c.3991+125C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 886,292 control chromosomes in the GnomAD database, including 50,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11442 hom., cov: 33)

Exomes 𝑓: 0.32 ( 38791 hom. )

Consequence

LRP1
NM_002332.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 12-57176231-C-A is Benign according to our data. Variant chr12-57176231-C-A is described in ClinVar as [Benign]. Clinvar id is 1260371.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1	NM_002332.3 linkuse as main transcript	c.3991+125C>A		intron_variant		ENST00000243077.8	NP_002323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8 linkuse as main transcript	c.3991+125C>A		intron_variant		1	NM_002332.3	ENSP00000243077	P1	Q07954-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57423

AN:

152096

Hom.:

11414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.368

GnomAD4 exome

AF:

0.317

AC:

232547

AN:

734076

Hom.:

38791

AF XY:

0.311

AC XY:

117243

AN XY:

376984

show subpopulations

Gnomad4 AFR exome

AF:

0.480

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.300

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.397

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.378

AC:

57496

AN:

152216

Hom.:

11442

Cov.:

AF XY:

0.377

AC XY:

28039

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.486

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.328

Hom.:

7944

Bravo

AF:

0.394

Asia WGS

AF:

0.412

AC:

1432

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.85

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