chr12-10160401-C-G

Variant names:

• chr12-10160401-C-G
• rs373022812
• NM_002543.4:c.626G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002543.4(OLR1):​c.626G>C​(p.Arg209Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R209K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLR1 NM_002543.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12901944).

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.626G>C	p.Arg209Thr	missense	Exon 5 of 6	NP_002534.1	P78380-1
	OLR1	NM_001172632.2		c.486G>C	p.Glu162Asp	missense	Exon 4 of 5	NP_001166103.1	P78380-2
	OLR1	NM_001172633.2		c.565-380G>C		intron	N/A	NP_001166104.1	P78380-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	ENST00000309539.8	TSL:1 MANE Select	c.626G>C	p.Arg209Thr	missense	Exon 5 of 6	ENSP00000309124.3	P78380-1
	OLR1	ENST00000896632.1		c.614G>C	p.Arg205Thr	missense	Exon 5 of 6	ENSP00000566691.1
	OLR1	ENST00000539518.5	TSL:2	c.467G>C	p.Arg156Thr	missense	Exon 4 of 5	ENSP00000442389.1	F5H7N8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461662 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727088

⚠️ 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: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60388

⚠️ 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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.5
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.39
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.044
Sift	Benign	0.039	D
Sift4G	Benign	0.33	T
Vest4		0.32
MutPred		0.20		Gain of catalytic residue at A159 (P = 9e-04)
MVP		0.15
ClinPred		0.19	T
GERP RS		-0.59
Varity_R		0.23
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs373022812; hg19: chr12-10313000;