12-10160049-C-T

Variant names:

• chr12-10160049-C-T
• rs13306593
• NM_002543.4:c.681-28G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002543.4(OLR1):​c.681-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.681-28G>A		intron	N/A	NP_002534.1	P78380-1
	OLR1	NM_001172633.2		c.565-28G>A		intron	N/A	NP_001166104.1	P78380-3
	OLR1	NM_001172632.2		c.541-28G>A		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.681-28G>A		intron	N/A	ENSP00000309124.3	P78380-1
	OLR1	ENST00000896632.1		c.669-28G>A		intron	N/A	ENSP00000566691.1
	OLR1	ENST00000539518.5	TSL:2	c.522-28G>A		intron	N/A	ENSP00000442389.1	F5H7N8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1421594 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 702956

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31756

American (AMR) AF: 0.00 AC: 0 AN: 37698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24514

East Asian (EAS) AF: 0.00 AC: 0 AN: 39040

South Asian (SAS) AF: 0.00 AC: 0 AN: 82224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091150

Other (OTH) AF: 0.00 AC: 0 AN: 58458

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		-0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13306593; hg19: chr12-10312648;