12-10160476-T-C

Position:

• chr12-10160476-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000309539.8(OLR1):​c.565-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,584,552 control chromosomes in the GnomAD database, including 171,160 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 (13734 hom., cov: 31)
  • Exomes 𝑓: 0.46 (157426 hom.)
• Consequence: OLR1 ENST00000309539.8 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLR1	NM_002543.4	c.565-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000309539.8	NP_002534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLR1	ENST00000309539.8	c.565-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002543.4	ENSP00000309124	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61065 AN: 151820 Hom.: 13731 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.460

GnomAD3 exomes AF: 0.435 AC: 104299 AN: 239886 Hom.: 24028 AF XY: 0.434 AC XY: 56120 AN XY: 129424

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.302

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.485

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.461 AC: 660734 AN: 1432614 Hom.: 157426 Cov.: 25 AF XY: 0.459 AC XY: 327291 AN XY: 713658

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.402 AC: 61077 AN: 151938 Hom.: 13734 Cov.: 31 AF XY: 0.402 AC XY: 29828 AN XY: 74262

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.456

Alfa AF: 0.461 Hom.: 3742

Bravo AF: 0.399

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3736235; hg19: chr12-10313075; COSMIC: COSV58871643; COSMIC: COSV58871643;