Variant 12-57196975-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 NM_002332.3(LRP1):c.8893-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,602,714 control chromosomes in the GnomAD database, including 90,575 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11790 hom., cov: 33)

Exomes 𝑓: 0.32 ( 78785 hom. )

Consequence

LRP1
NM_002332.3 splice_region, intron

Scores

Splicing: ADA: 0.0002673

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.664

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=-0.66).

BP6

Variant 12-57196975-C-T is Benign according to our data. Variant chr12-57196975-C-T is described in ClinVar as [Benign]. Clinvar id is 1252707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 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.8893-7C>T		splice_region_variant, intron_variant		ENST00000243077.8	NP_002323.2	Q07954-1Q59FG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8 linkuse as main transcript	c.8893-7C>T		splice_region_variant, intron_variant		1	NM_002332.3	ENSP00000243077.3		Q07954-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58135

AN:

151856

Hom.:

11763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.372

GnomAD3 exomes

AF:

0.358

AC:

83732

AN:

234050

Hom.:

16011

AF XY:

0.338

AC XY:

43133

AN XY:

127640

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.445

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.323

AC:

468837

AN:

1450740

Hom.:

78785

Cov.:

AF XY:

0.317

AC XY:

229035

AN XY:

721810

show subpopulations

Gnomad4 AFR exome

AF:

0.509

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.398

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.383

AC:

58210

AN:

151974

Hom.:

11790

Cov.:

AF XY:

0.382

AC XY:

28396

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.457

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.341

Hom.:

3756

Bravo

AF:

0.400

Asia WGS

AF:

0.412

AC:

1431

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Keratosis pilaris

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.5

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.0

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