Variant chr12-57167668-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000243077.8(LRP1):c.2995+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 659,218 control chromosomes in the GnomAD database, including 47,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17325 hom., cov: 33)

Exomes 𝑓: 0.33 ( 30569 hom. )

Consequence

LRP1
ENST00000243077.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.81

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-57167668-C-T is Benign according to our data. Variant chr12-57167668-C-T is described in ClinVar as [Benign]. Clinvar id is 1269528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 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.2995+144C>T		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.2995+144C>T		intron_variant		1	NM_002332.3	ENSP00000243077	P1	Q07954-1
LRP1	ENST00000553446.1 linkuse as main transcript	n.80+144C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67300

AN:

151916

Hom.:

17287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.408

GnomAD4 exome

AF:

0.333

AC:

169038

AN:

507184

Hom.:

30569

AF XY:

0.323

AC XY:

87161

AN XY:

269602

show subpopulations

Gnomad4 AFR exome

AF:

0.709

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.398

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.398

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.443

AC:

67391

AN:

152034

Hom.:

17325

Cov.:

AF XY:

0.440

AC XY:

32718

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.713

Gnomad4 AMR

AF:

0.419

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.373

Hom.:

2966

Bravo

AF:

0.468

Asia WGS

AF:

0.426

AC:

1478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.48

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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