Variant 12-57191361-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002332.3(LRP1):c.7278C>T(p.Ala2426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,611,140 control chromosomes in the GnomAD database, including 358,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 26299 hom., cov: 32)

Exomes 𝑓: 0.67 ( 332152 hom. )

Consequence

LRP1
NM_002332.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.92

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 12-57191361-C-T is Benign according to our data. Variant chr12-57191361-C-T is described in ClinVar as [Benign]. Clinvar id is 1236943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57191361-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 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.7278C>T	p.Ala2426=	synonymous_variant	44/89	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.7278C>T	p.Ala2426=	synonymous_variant	44/89	1	NM_002332.3	ENSP00000243077	P1	Q07954-1
LRP1	ENST00000554118.1 linkuse as main transcript	c.293+352C>T		intron_variant		2		ENSP00000451622

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86012

AN:

151802

Hom.:

26299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.593

GnomAD3 exomes

AF:

0.623

AC:

155855

AN:

250068

Hom.:

50642

AF XY:

0.646

AC XY:

87329

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.548

Gnomad SAS exome

AF:

0.787

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.670

AC:

977287

AN:

1459220

Hom.:

332152

Cov.:

AF XY:

0.676

AC XY:

490628

AN XY:

725454

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.683

Gnomad4 EAS exome

AF:

0.588

Gnomad4 SAS exome

AF:

0.785

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.686

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.566

AC:

86023

AN:

151920

Hom.:

26299

Cov.:

AF XY:

0.569

AC XY:

42233

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.325

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.678

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.764

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.684

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.656

Hom.:

58010

Bravo

AF:

0.543

Asia WGS

AF:

0.570

AC:

1985

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.691

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	clinical testing	GeneDx	Jun 02, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.59

CADD

Benign

0.13

DANN

Benign

0.89

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