rs11053646

chr12-10160849-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1541 hom., cov: 32)
  • Exomes 𝑓: 0.099 (8607 hom.)
• Consequence: OLR1 NM_002543.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.0190

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]

ACMG classification

Verdict is Benign. Variant got -14 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]. Clinvar id is 6994.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
OLR1	NM_002543.4	c.501G>C	p.Lys167Asn	missense_variant	4/6	ENST00000309539.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLR1	ENST00000309539.8	c.501G>C	p.Lys167Asn	missense_variant	4/6	1	NM_002543.4	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19128 AN: 152050 Hom.: 1539 Cov.: 32

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

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.: 33 AF XY: 0.101 AC XY: 73649 AN XY: 727132

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.: 32 AF XY: 0.125 AC XY: 9333 AN XY: 74398

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

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

OLR1-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	17
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	N
LIST_S2	Benign	0.74	T;T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L;L;.;.;.
MutationTaster	Benign	0.12	P;P;P;P;P
PrimateAI	Benign	0.43	T
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	T
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

Other links and lift over

dbSNP: rs11053646; hg19: chr12-10313448; COSMIC: COSV58871619; COSMIC: COSV58871619;