Variant 12-10160849-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002543.4(OLR1):c.501G>C(p.Lys167Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,828 control chromosomes in the GnomAD database, including 10,148 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1541 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8607 hom. )

Consequence

OLR1
NM_002543.4 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.0190

Variant links:

Genes affected

OLR1 (HGNC:8133): (oxidized low density lipoprotein receptor 1) This gene encodes a low density lipoprotein receptor that belongs to the C-type lectin superfamily. This gene is regulated through the cyclic AMP signaling pathway. The encoded protein binds, internalizes and degrades oxidized low-density lipoprotein. This protein may be involved in the regulation of Fas-induced apoptosis. This protein may play a role as a scavenger receptor. Mutations of this gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

OLR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001839906).

BP6

Variant 12-10160849-C-G is Benign according to our data. Variant chr12-10160849-C-G is described in ClinVar as [Benign, risk_factor]. Clinvar id is 6994.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLR1	NM_002543.4 linkuse as main transcript	c.501G>C	p.Lys167Asn	missense_variant	4/6	ENST00000309539.8	NP_002534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLR1	ENST00000309539.8 linkuse as main transcript	c.501G>C	p.Lys167Asn	missense_variant	4/6	1	NM_002543.4	ENSP00000309124	P1	P78380-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19128

AN:

152050

Hom.:

1539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.0797

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0872

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.108

AC:

27102

AN:

251394

Hom.:

1922

AF XY:

0.111

AC XY:

15106

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0373

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.0833

Gnomad NFE exome

AF:

0.0904

Gnomad OTH exome

AF:

0.0843

GnomAD4 exome

AF:

0.0993

AC:

145143

AN:

1461660

Hom.:

8607

Cov.:

AF XY:

0.101

AC XY:

73649

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.0396

Gnomad4 ASJ exome

AF:

0.0449

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.0862

Gnomad4 NFE exome

AF:

0.0892

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.126

AC:

19149

AN:

152168

Hom.:

1541

Cov.:

AF XY:

0.125

AC XY:

9333

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.0604

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.0797

Gnomad4 NFE

AF:

0.0872

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0921

Hom.:

572

Bravo

AF:

0.127

TwinsUK

AF:

0.0917

AC:

340

ALSPAC

AF:

0.0820

AC:

316

ESP6500AA

AF:

0.209

AC:

919

ESP6500EA

AF:

0.0908

AC:

781

ExAC

AF:

0.115

AC:

13967

Asia WGS

AF:

0.190

AC:

658

AN:

3478

EpiCase

AF:

0.0797

EpiControl

AF:

0.0844

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OLR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Myocardial infarction, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 28, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.064

T;.;.;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.74

T;T;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;L;.;.;.

MutationTaster

Benign

0.12

P;P;P;P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.78

N;N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;.;.

Polyphen

0.63

P;.;.;.;.

Vest4

0.28

MutPred

0.23

Loss of ubiquitination at K167 (P = 0.0059);Loss of ubiquitination at K167 (P = 0.0059);.;.;.;

MPC

0.37

ClinPred

0.015

GERP RS

-0.21

Varity_R

0.38

gMVP

0.38

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