rs3912640

Variant names:

• chr12-10167613-C-T
• rs3912640
• NM_002543.4:c.179-656G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002543.4(OLR1):​c.179-656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,108 control chromosomes in the GnomAD database, including 1,718 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 0.12 (1718 hom., cov: 31)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: OLR1 NM_002543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 7 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 -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 = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLR1	NM_002543.4	c.179-656G>A		intron_variant	Intron 2 of 5	ENST00000309539.8	NP_002534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLR1	ENST00000309539.8	c.179-656G>A		intron_variant	Intron 2 of 5	1	NM_002543.4	ENSP00000309124.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18518 AN: 151966 Hom.: 1711 Cov.: 31

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0909 AC: 2 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.122 AC: 18534 AN: 152084 Hom.: 1718 Cov.: 31 AF XY: 0.129 AC XY: 9612 AN XY: 74302

African (AFR) AF: 0.0278 AC: 1154 AN: 41516

American (AMR) AF: 0.164 AC: 2496 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 314 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1931 AN: 5162

South Asian (SAS) AF: 0.302 AC: 1453 AN: 4818

European-Finnish (FIN) AF: 0.168 AC: 1769 AN: 10534

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8938 AN: 67996

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.133 Hom.: 2831

Bravo AF: 0.117

Asia WGS AF: 0.340 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.75
PhyloP100		0.040
PromoterAI		-0.047	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3912640; hg19: chr12-10320212;