12-10170283-G-T

Position:

• chr12-10170283-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLR1	NM_002543.4	c.77-1108C>A		intron_variant		ENST00000309539.8	NP_002534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLR1	ENST00000309539.8	c.77-1108C>A		intron_variant		1	NM_002543.4	ENSP00000309124	P1

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

Gnomad4 NFE exome AF: 0.250

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

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.356

Alfa AF: 0.333 Hom.: 14905

Bravo AF: 0.402

Asia WGS AF: 0.501 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2742113; hg19: chr12-10322882;