12-10159363-T-G

Variant names:

• chr12-10159363-T-G
• rs10505755
• NM_002543.4:c.*517A>C

Variant summary

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

The NM_002543.4(OLR1):​c.*517A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 153,004 control chromosomes in the GnomAD database, including 13,877 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 (13743 hom., cov: 31)
  • Exomes 𝑓: 0.43 (134 hom.)
• Consequence: OLR1 NM_002543.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 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.*517A>C		3_prime_UTR	Exon 6 of 6	NP_002534.1
	OLR1	NM_001172633.2		c.*653A>C		3_prime_UTR	Exon 5 of 5	NP_001166104.1
	OLR1	NM_001172632.2		c.*653A>C		3_prime_UTR	Exon 5 of 5	NP_001166103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	ENST00000309539.8	TSL:1 MANE Select	c.*517A>C		3_prime_UTR	Exon 6 of 6	ENSP00000309124.3
	OLR1	ENST00000544577.5	TSL:5	c.*517A>C		downstream_gene	N/A	ENSP00000444457.1
	OLR1	ENST00000543993.5	TSL:2	c.*653A>C		downstream_gene	N/A	ENSP00000445085.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61046 AN: 151648 Hom.: 13740 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.575

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: 0.461

GnomAD4 exome AF: 0.427 AC: 529 AN: 1238 Hom.: 134 Cov.: 0 AF XY: 0.426 AC XY: 287 AN XY: 674

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.431 AC: 87 AN: 202

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 2 AN: 6

East Asian (EAS) AF: 0.250 AC: 7 AN: 28

South Asian (SAS) AF: 0.255 AC: 26 AN: 102

European-Finnish (FIN) AF: 0.564 AC: 114 AN: 202

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.426 AC: 289 AN: 678

Other (OTH) AF: 0.188 AC: 3 AN: 16

GnomAD4 genome AF: 0.402 AC: 61058 AN: 151766 Hom.: 13743 Cov.: 31 AF XY: 0.402 AC XY: 29798 AN XY: 74124

African (AFR) AF: 0.209 AC: 8634 AN: 41340

American (AMR) AF: 0.522 AC: 7966 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1191 AN: 5148

South Asian (SAS) AF: 0.287 AC: 1378 AN: 4808

European-Finnish (FIN) AF: 0.494 AC: 5182 AN: 10488

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

European-Non Finnish (NFE) AF: 0.488 AC: 33170 AN: 67950

Other (OTH) AF: 0.457 AC: 959 AN: 2100

Alfa AF: 0.460 Hom.: 29032

Bravo AF: 0.399

Asia WGS AF: 0.257 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		0.083
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: rs10505755; hg19: chr12-10311962;