chr12-10160092-T-C

Variant names:

• chr12-10160092-T-C
• rs17174597
• NM_002543.4:c.681-71A>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.681-71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,505,810 control chromosomes in the GnomAD database, including 160,697 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: 33)
  • Exomes 𝑓: 0.46 (146954 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 7 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=-0.83).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	NM_002543.4	MANE Select	c.681-71A>G		intron	N/A	NP_002534.1	P78380-1
	OLR1	NM_001172633.2		c.565-71A>G		intron	N/A	NP_001166104.1	P78380-3
	OLR1	NM_001172632.2		c.541-71A>G		intron	N/A	NP_001166103.1	P78380-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	ENST00000309539.8	TSL:1 MANE Select	c.681-71A>G		intron	N/A	ENSP00000309124.3	P78380-1
	OLR1	ENST00000896632.1		c.669-71A>G		intron	N/A	ENSP00000566691.1
	OLR1	ENST00000539518.5	TSL:2	c.522-71A>G		intron	N/A	ENSP00000442389.1	F5H7N8

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61100 AN: 151972 Hom.: 13740 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.454

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: 0.460

GnomAD4 exome AF: 0.458 AC: 619481 AN: 1353720 Hom.: 146954 AF XY: 0.455 AC XY: 304901 AN XY: 669602

African (AFR) AF: 0.196 AC: 5922 AN: 30226

American (AMR) AF: 0.516 AC: 17054 AN: 33040

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 13370 AN: 22648

East Asian (EAS) AF: 0.207 AC: 8026 AN: 38726

South Asian (SAS) AF: 0.302 AC: 23104 AN: 76486

European-Finnish (FIN) AF: 0.486 AC: 21810 AN: 44872

Middle Eastern (MID) AF: 0.509 AC: 2723 AN: 5352

European-Non Finnish (NFE) AF: 0.480 AC: 502327 AN: 1046460

Other (OTH) AF: 0.450 AC: 25145 AN: 55910

GnomAD4 genome AF: 0.402 AC: 61112 AN: 152090 Hom.: 13743 Cov.: 33 AF XY: 0.401 AC XY: 29847 AN XY: 74350

African (AFR) AF: 0.208 AC: 8650 AN: 41504

American (AMR) AF: 0.522 AC: 7978 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1997 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1197 AN: 5172

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4828

European-Finnish (FIN) AF: 0.494 AC: 5209 AN: 10542

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

European-Non Finnish (NFE) AF: 0.488 AC: 33155 AN: 67966

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

Alfa AF: 0.432 Hom.: 1963

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	-0.83
CADD	Benign	8.6
DANN	Benign	0.82
PhyloP100		-0.014
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: rs17174597; hg19: chr12-10312691;