12-57147482-C-T

Position:

• chr12-57147482-C-T

Variant summary

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

The NM_002332.3(LRP1):​c.841+1992C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,144 control chromosomes in the GnomAD database, including 2,860 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 0.18 (2857 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3 hom.)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

LRP1 (HGNC:6692): (LDL receptor related protein 1) This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015]

LRP1-AS (HGNC:51694): (LRP1 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1	NM_002332.3	c.841+1992C>T		intron_variant		ENST00000243077.8
LRP1-AS	NR_131938.1	n.138G>A		non_coding_transcript_exon_variant	1/2
LRP1-AS	NR_131939.1	n.138G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1	ENST00000243077.8	c.841+1992C>T		intron_variant		1	NM_002332.3	P1
LRP1-AS	ENST00000555461.1	n.138G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27671 AN: 151878 Hom.: 2851 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.128 AC: 19 AN: 148 Hom.: 3 Cov.: 0 AF XY: 0.102 AC XY: 11 AN XY: 108

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.182 AC: 27707 AN: 151996 Hom.: 2857 Cov.: 32 AF XY: 0.184 AC XY: 13670 AN XY: 74314

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.189

Alfa AF: 0.149 Hom.: 1763

Bravo AF: 0.187

Asia WGS AF: 0.251 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.1
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306692; hg19: chr12-57541265;