NM_002543.4:c.565-14A>G

Variant names:

• chr12-10160476-T-C
• rs3736235
• NM_002543.4:c.565-14A>G

Variant summary

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

The NM_002543.4(OLR1):​c.565-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,584,552 control chromosomes in the GnomAD database, including 171,160 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 (13734 hom., cov: 31)
  • Exomes 𝑓: 0.46 (157426 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• Publications: 18 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=-0.93).
• 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 rank	MANE	Protein	UniProt
OLR1	NM_002543.4	c.565-14A>G		intron_variant	Intron 4 of 5	ENST00000309539.8	NP_002534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLR1	ENST00000309539.8	c.565-14A>G		intron_variant	Intron 4 of 5	1	NM_002543.4	ENSP00000309124.3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61065 AN: 151820 Hom.: 13731 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.576

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: 0.460

GnomAD2 exomes AF: 0.435 AC: 104299 AN: 239886 AF XY: 0.434

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.485

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.461 AC: 660734 AN: 1432614 Hom.: 157426 Cov.: 25 AF XY: 0.459 AC XY: 327291 AN XY: 713658

African (AFR) AF: 0.201 AC: 6579 AN: 32794

American (AMR) AF: 0.517 AC: 22296 AN: 43122

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 15231 AN: 25706

East Asian (EAS) AF: 0.208 AC: 8213 AN: 39472

South Asian (SAS) AF: 0.307 AC: 26032 AN: 84916

European-Finnish (FIN) AF: 0.490 AC: 26015 AN: 53068

Middle Eastern (MID) AF: 0.514 AC: 2943 AN: 5728

European-Non Finnish (NFE) AF: 0.484 AC: 526526 AN: 1088450

Other (OTH) AF: 0.453 AC: 26899 AN: 59358

GnomAD4 genome AF: 0.402 AC: 61077 AN: 151938 Hom.: 13734 Cov.: 31 AF XY: 0.402 AC XY: 29828 AN XY: 74262

African (AFR) AF: 0.208 AC: 8634 AN: 41422

American (AMR) AF: 0.522 AC: 7961 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1192 AN: 5148

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4822

European-Finnish (FIN) AF: 0.494 AC: 5212 AN: 10548

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33152 AN: 67958

Other (OTH) AF: 0.456 AC: 964 AN: 2112

Alfa AF: 0.456 Hom.: 3761

Bravo AF: 0.399

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3736235; hg19: chr12-10313075; COSMIC: COSV58871643; COSMIC: COSV58871643;