12-10160535-G-A

Variant names:

• chr12-10160535-G-A
• rs3736234
• NM_002543.4:c.565-73C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002543.4(OLR1):​c.565-73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,238,012 control chromosomes in the GnomAD database, including 129,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13741 hom., cov: 32)
  • Exomes 𝑓: 0.45 (115800 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.512
• Publications: 18 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-10160535-G-A is Benign according to our data. Variant chr12-10160535-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	NM_002543.4	MANE Select	c.565-73C>T		intron	N/A	NP_002534.1
	OLR1	NM_001172633.2		c.564+251C>T		intron	N/A	NP_001166104.1
	OLR1	NM_001172632.2		c.425-73C>T		intron	N/A	NP_001166103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLR1	ENST00000309539.8	TSL:1 MANE Select	c.565-73C>T		intron	N/A	ENSP00000309124.3
	OLR1	ENST00000536989.1	TSL:2	n.27C>T		non_coding_transcript_exon	Exon 1 of 2
	OLR1	ENST00000539518.5	TSL:2	c.406-73C>T		intron	N/A	ENSP00000442389.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61079 AN: 151806 Hom.: 13738 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.452 AC: 490997 AN: 1086088 Hom.: 115800 Cov.: 14 AF XY: 0.449 AC XY: 247466 AN XY: 551160

African (AFR) AF: 0.201 AC: 5153 AN: 25664

American (AMR) AF: 0.517 AC: 17597 AN: 34004

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 13067 AN: 22106

East Asian (EAS) AF: 0.206 AC: 7537 AN: 36588

South Asian (SAS) AF: 0.305 AC: 22701 AN: 74396

European-Finnish (FIN) AF: 0.490 AC: 24752 AN: 50530

Middle Eastern (MID) AF: 0.506 AC: 2531 AN: 5004

European-Non Finnish (NFE) AF: 0.476 AC: 376267 AN: 790146

Other (OTH) AF: 0.449 AC: 21392 AN: 47650

GnomAD4 genome AF: 0.402 AC: 61091 AN: 151924 Hom.: 13741 Cov.: 32 AF XY: 0.402 AC XY: 29835 AN XY: 74242

African (AFR) AF: 0.209 AC: 8646 AN: 41418

American (AMR) AF: 0.521 AC: 7960 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1996 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1199 AN: 5180

South Asian (SAS) AF: 0.287 AC: 1380 AN: 4812

European-Finnish (FIN) AF: 0.495 AC: 5210 AN: 10520

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33158 AN: 67952

Other (OTH) AF: 0.457 AC: 964 AN: 2110

Alfa AF: 0.453 Hom.: 8498

Bravo AF: 0.399

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25904137)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	17
DANN	Benign	0.71
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -20

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

Other links and lift over

dbSNP: rs3736234; hg19: chr12-10313134; COSMIC: COSV58871646; COSMIC: COSV58871646;