NM_002543.4:c.317T>C

Variant names:

• chr12-10166819-A-G
• rs1403128339
• NM_002543.4:c.317T>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.317T>C​(p.Ile106Thr) 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 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLR1 NM_002543.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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=0.20284066).

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.317T>C	p.Ile106Thr	missense	Exon 3 of 6	NP_002534.1	P78380-1
	OLR1	NM_001172633.2		c.317T>C	p.Ile106Thr	missense	Exon 3 of 5	NP_001166104.1	P78380-3
	OLR1	NM_001172632.2		c.317T>C	p.Ile106Thr	missense	Exon 3 of 5	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.317T>C	p.Ile106Thr	missense	Exon 3 of 6	ENSP00000309124.3	P78380-1
	OLR1	ENST00000896632.1		c.317T>C	p.Ile106Thr	missense	Exon 3 of 6	ENSP00000566691.1
	OLR1	ENST00000539518.5	TSL:2	c.158T>C	p.Ile53Thr	missense	Exon 2 of 5	ENSP00000442389.1	F5H7N8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.094
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.48	P
Vest4		0.47
MutPred		0.49		Gain of phosphorylation at I106 (P = 0.069)
MVP		0.41
MPC		0.37
ClinPred		0.61	D
GERP RS		2.5
PromoterAI		0.025	Neutral
Varity_R		0.11
gMVP		0.33
Mutation Taster		=94/6	polymorphism

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: rs1403128339; hg19: chr12-10319418;