12-10160666-C-T

Variant names:

• chr12-10160666-C-T
• rs3736233
• NM_002543.4:c.564+120G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002543.4(OLR1):​c.564+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,332,176 control chromosomes in the GnomAD database, including 138,032 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 (13737 hom., cov: 32)
  • Exomes 𝑓: 0.45 (124295 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002543.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	NM_002543.4	MANE Select	c.564+120G>A		intron	N/A	NP_002534.1
	OLR1	NM_001172633.2		c.564+120G>A		intron	N/A	NP_001166104.1
	OLR1	NM_001172632.2		c.425-204G>A		intron	N/A	NP_001166103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	ENST00000309539.8	TSL:1 MANE Select	c.564+120G>A		intron	N/A	ENSP00000309124.3
	OLR1	ENST00000539518.5	TSL:2	c.405+120G>A		intron	N/A	ENSP00000442389.1
	OLR1	ENST00000545927.5	TSL:2	c.564+120G>A		intron	N/A	ENSP00000439251.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61078 AN: 151900 Hom.: 13734 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.450 AC: 531534 AN: 1180160 Hom.: 124295 Cov.: 16 AF XY: 0.448 AC XY: 264471 AN XY: 589758

African (AFR) AF: 0.196 AC: 5440 AN: 27698

American (AMR) AF: 0.516 AC: 19576 AN: 37940

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 12107 AN: 20574

East Asian (EAS) AF: 0.207 AC: 7883 AN: 38112

South Asian (SAS) AF: 0.302 AC: 21217 AN: 70180

European-Finnish (FIN) AF: 0.488 AC: 23726 AN: 48660

Middle Eastern (MID) AF: 0.509 AC: 2352 AN: 4620

European-Non Finnish (NFE) AF: 0.473 AC: 416752 AN: 881930

Other (OTH) AF: 0.446 AC: 22481 AN: 50446

GnomAD4 genome AF: 0.402 AC: 61089 AN: 152016 Hom.: 13737 Cov.: 32 AF XY: 0.402 AC XY: 29852 AN XY: 74318

African (AFR) AF: 0.208 AC: 8646 AN: 41480

American (AMR) AF: 0.522 AC: 7960 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1995 AN: 3466

East Asian (EAS) AF: 0.230 AC: 1191 AN: 5182

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4826

European-Finnish (FIN) AF: 0.494 AC: 5210 AN: 10548

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33158 AN: 67944

Other (OTH) AF: 0.456 AC: 963 AN: 2112

Alfa AF: 0.453 Hom.: 8509

Bravo AF: 0.399

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.55
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3736233; hg19: chr12-10313265; COSMIC: COSV58871652; COSMIC: COSV58871652;