chr12-57146968-C-G

Position:

• chr12-57146968-C-G

Variant summary

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

The NM_002332.3(LRP1):​c.841+1478C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,860 control chromosomes in the GnomAD database, including 19,446 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 0.50 (19446 hom., cov: 31)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1	NM_002332.3	c.841+1478C>G		intron_variant		ENST00000243077.8	NP_002323.2
LRP1-AS	NR_131938.1	n.181+471G>C		intron_variant, non_coding_transcript_variant
LRP1-AS	NR_131939.1	n.182-245G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1	ENST00000243077.8	c.841+1478C>G		intron_variant		1	NM_002332.3	ENSP00000243077	P1
LRP1-AS	ENST00000555461.1	n.181+471G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76585 AN: 151742 Hom.: 19428 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.505 AC: 76646 AN: 151860 Hom.: 19446 Cov.: 31 AF XY: 0.507 AC XY: 37616 AN XY: 74220

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.497

Alfa AF: 0.517 Hom.: 2500

Bravo AF: 0.503

Asia WGS AF: 0.422 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.81

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: rs7968719; hg19: chr12-57540751;