rs11837145

chr12-57176231-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002332.3(LRP1):c.3991+125C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 886,292 control chromosomes in the GnomAD database, including 50,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11442 hom., cov: 33)
  • Exomes 𝑓: 0.32 (38791 hom.)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 12-57176231-C-A is Benign according to our data. Variant chr12-57176231-C-A is described in ClinVar as [Benign]. Clinvar id is 1260371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1	NM_002332.3	c.3991+125C>A		intron_variant		ENST00000243077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1	ENST00000243077.8	c.3991+125C>A		intron_variant		1	NM_002332.3	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57423 AN: 152096 Hom.: 11414 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.317 AC: 232547 AN: 734076 Hom.: 38791 AF XY: 0.311 AC XY: 117243 AN XY: 376984

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.378 AC: 57496 AN: 152216 Hom.: 11442 Cov.: 33 AF XY: 0.377 AC XY: 28039 AN XY: 74424

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.367

Alfa AF: 0.328 Hom.: 7944

Bravo AF: 0.394

Asia WGS AF: 0.412 AC: 1432 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	-0.44
Cadd	Benign	17
Dann	Benign	0.85

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: rs11837145; hg19: chr12-57570014;