NM_002543.4:c.77-1108C>A

Variant names:

• chr12-10170283-G-T
• rs2742113
• NM_002543.4:c.77-1108C>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.77-1108C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,932 control chromosomes in the GnomAD database, including 12,765 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 (12765 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 10 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]

TMEM52B (HGNC:26438): (transmembrane protein 52B) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 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.77-1108C>A		intron	N/A	NP_002534.1
	OLR1	NM_001172633.2		c.77-1108C>A		intron	N/A	NP_001166104.1
	OLR1	NM_001172632.2		c.77-1108C>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.77-1108C>A		intron	N/A	ENSP00000309124.3
	OLR1	ENST00000545927.5	TSL:2	c.77-1108C>A		intron	N/A	ENSP00000439251.1
	OLR1	ENST00000432556.6	TSL:2	c.77-1108C>A		intron	N/A	ENSP00000405116.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60237 AN: 151808 Hom.: 12745 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.397 AC: 60296 AN: 151928 Hom.: 12765 Cov.: 32 AF XY: 0.400 AC XY: 29698 AN XY: 74216

African (AFR) AF: 0.542 AC: 22442 AN: 41416

American (AMR) AF: 0.354 AC: 5394 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3464

East Asian (EAS) AF: 0.561 AC: 2890 AN: 5156

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4816

European-Finnish (FIN) AF: 0.359 AC: 3783 AN: 10540

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21532 AN: 67960

Other (OTH) AF: 0.356 AC: 752 AN: 2112

Alfa AF: 0.346 Hom.: 36541

Bravo AF: 0.402

Asia WGS AF: 0.501 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.56
PhyloP100		-0.48
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2742113; hg19: chr12-10322882;