chr12-10160049-C-A

Position:

• chr12-10160049-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002543.4(OLR1):​c.681-28G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,572,126 control chromosomes in the GnomAD database, including 169,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (13703 hom., cov: 32)
  • Exomes 𝑓: 0.46 (155447 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• 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.681-28G>T		intron_variant		ENST00000309539.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLR1	ENST00000309539.8	c.681-28G>T		intron_variant		1	NM_002543.4	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61012 AN: 151786 Hom.: 13700 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.459

GnomAD3 exomes AF: 0.432 AC: 98568 AN: 228326 Hom.: 22731 AF XY: 0.431 AC XY: 53717 AN XY: 124542

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.587

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.299

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.484

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.460 AC: 653560 AN: 1420224 Hom.: 155447 Cov.: 34 AF XY: 0.458 AC XY: 321329 AN XY: 702306

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.402 AC: 61023 AN: 151902 Hom.: 13703 Cov.: 32 AF XY: 0.401 AC XY: 29788 AN XY: 74230

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.455

Alfa AF: 0.441 Hom.: 1984

Bravo AF: 0.398

Asia WGS AF: 0.256 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.22

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: rs13306593; hg19: chr12-10312648; COSMIC: COSV58873026; COSMIC: COSV58873026;