rs144902096

Variant names:

• chr12-57138565-C-T
• rs144902096
• NM_002332.3:c.174C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57138565-C-T
• chr12-57138565-C-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_002332.3(LRP1):​c.174C>T​(p.Asp58Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: LRP1 NM_002332.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• keratosis follicularis spinulosa decalvans

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• atrophoderma vermiculata

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• developmental dysplasia of the hip 3

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• keratosis pilaris atrophicans

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 12-57138565-C-T is Benign according to our data. Variant chr12-57138565-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643111.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	NM_002332.3	MANE Select	c.174C>T	p.Asp58Asp	synonymous	Exon 2 of 89	NP_002323.2	Q07954-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1	ENST00000243077.8	TSL:1 MANE Select	c.174C>T	p.Asp58Asp	synonymous	Exon 2 of 89	ENSP00000243077.3	Q07954-1
	LRP1	ENST00000554174.1	TSL:1	c.174C>T	p.Asp58Asp	synonymous	Exon 2 of 8	ENSP00000451737.1	Q6PJ72
	LRP1	ENST00000553277.5	TSL:1	c.174C>T	p.Asp58Asp	synonymous	Exon 2 of 7	ENSP00000451449.1	Q7Z7K9

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152164 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000370 AC: 93 AN: 251274 AF XY: 0.000346

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00626

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000178 AC: 260 AN: 1461734 Hom.: 0 Cov.: 31 AF XY: 0.000186 AC XY: 135 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00563 AC: 147 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86250

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111916

Other (OTH) AF: 0.000480 AC: 29 AN: 60382

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152282 Hom.: 1 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74452

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.000719 AC: 11 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000381 Hom.: 0

Bravo AF: 0.000329

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	3.1
DANN	Benign	0.86
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs144902096; hg19: chr12-57532348;