Genetic Variant OLR1:c.77-1108C>A (chr12-10170283-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.477

Publications

10 publications found

Variant links:

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]

OLR1 links:

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

TMEM52B links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OLR1	NM_002543.4	MANE Select	c.77-1108C>A	intron	N/A	NP_002534.1	P78380-1
OLR1	NM_001172633.2		c.77-1108C>A	intron	N/A	NP_001166104.1	P78380-3
OLR1	NM_001172632.2		c.77-1108C>A	intron	N/A	NP_001166103.1	P78380-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OLR1	ENST00000309539.8	TSL:1 MANE Select	c.77-1108C>A	intron	N/A	ENSP00000309124.3	P78380-1
OLR1	ENST00000896632.1		c.77-1108C>A	intron	N/A	ENSP00000566691.1
OLR1	ENST00000545927.5	TSL:2	c.77-1108C>A	intron	N/A	ENSP00000439251.1	P78380-3

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60237

AN:

151808

Hom.:

12745

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.397

AC:

60296

AN:

151928

Hom.:

12765

Cov.:

AF XY:

0.400

AC XY:

29698

AN XY:

74216

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21532

AN:

67960

Other (OTH)

AF:

0.356

AC:

752

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1783

3566

5349

7132

8915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.56

PhyloP100

-0.48

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over