rs1800174

chr12-57166026-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002332.3(LRP1):c.2672-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,612,696 control chromosomes in the GnomAD database, including 88,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11051 hom., cov: 33)
  • Exomes 𝑓: 0.32 (77513 hom.)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-57166026-G-A is Benign according to our data. Variant chr12-57166026-G-A is described in ClinVar as [Benign]. Clinvar id is 1242385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1	NM_002332.3	c.2672-58G>A		intron_variant		ENST00000243077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1	ENST00000243077.8	c.2672-58G>A		intron_variant		1	NM_002332.3	P1
LRP1	ENST00000556830.1	n.1519-58G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56570 AN: 152058 Hom.: 11037 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.320 AC: 467486 AN: 1460518 Hom.: 77513 Cov.: 37 AF XY: 0.314 AC XY: 228286 AN XY: 726402

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.372 AC: 56618 AN: 152178 Hom.: 11051 Cov.: 33 AF XY: 0.371 AC XY: 27599 AN XY: 74406

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.359

Alfa AF: 0.343 Hom.: 1497

Bravo AF: 0.387

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.42

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: rs1800174; hg19: chr12-57559809;