12-10169583-T-C

Variant names:

• chr12-10169583-T-C
• rs2742115
• NM_002543.4:c.77-408A>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.77-408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,128 control chromosomes in the GnomAD database, including 5,416 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 0.25 (5416 hom., cov: 32)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 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.77-408A>G		intron	N/A	NP_002534.1
	OLR1	NM_001172633.2		c.77-408A>G		intron	N/A	NP_001166104.1
	OLR1	NM_001172632.2		c.77-408A>G		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.77-408A>G		intron	N/A	ENSP00000309124.3
	OLR1	ENST00000545927.5	TSL:2	c.77-408A>G		intron	N/A	ENSP00000439251.1
	OLR1	ENST00000432556.6	TSL:2	c.77-408A>G		intron	N/A	ENSP00000405116.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37345 AN: 152010 Hom.: 5412 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37353 AN: 152128 Hom.: 5416 Cov.: 32 AF XY: 0.253 AC XY: 18829 AN XY: 74344

African (AFR) AF: 0.126 AC: 5241 AN: 41548

American (AMR) AF: 0.273 AC: 4174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3091 AN: 5168

South Asian (SAS) AF: 0.400 AC: 1926 AN: 4820

European-Finnish (FIN) AF: 0.326 AC: 3440 AN: 10544

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17934 AN: 67984

Other (OTH) AF: 0.245 AC: 517 AN: 2114

Alfa AF: 0.259 Hom.: 21989

Bravo AF: 0.236

Asia WGS AF: 0.470 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.085
DANN	Benign	0.64
PhyloP100		-1.8
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2742115; hg19: chr12-10322182;