12-10160535-G-A

Position:

• chr12-10160535-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002543.4(OLR1):​c.565-73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,238,012 control chromosomes in the GnomAD database, including 129,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (13741 hom., cov: 32)
  • Exomes 𝑓: 0.45 (115800 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.512

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 -10 ACMG points.

• BP6: Variant 12-10160535-G-A is Benign according to our data. Variant chr12-10160535-G-A is described in ClinVar as [Benign]. Clinvar id is 1227465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLR1	NM_002543.4	c.565-73C>T		intron_variant		ENST00000309539.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLR1	ENST00000309539.8	c.565-73C>T		intron_variant		1	NM_002543.4	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61079 AN: 151806 Hom.: 13738 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.452 AC: 490997 AN: 1086088 Hom.: 115800 Cov.: 14 AF XY: 0.449 AC XY: 247466 AN XY: 551160

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.402 AC: 61091 AN: 151924 Hom.: 13741 Cov.: 32 AF XY: 0.402 AC XY: 29835 AN XY: 74242

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.457

Alfa AF: 0.454 Hom.: 7607

Bravo AF: 0.399

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

This variant is associated with the following publications: (PMID: 25904137) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	17
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3736234; hg19: chr12-10313134; COSMIC: COSV58871646; COSMIC: COSV58871646;