rs7978567

Variant names:

• chr12-57202201-C-T
• rs7978567
• NM_002332.3:c.10595-220C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57202201-C-T
• chr12-57202201-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002332.3(LRP1):​c.10595-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,740 control chromosomes in the GnomAD database, including 11,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11971 hom., cov: 30)
• Consequence: LRP1 NM_002332.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234
• Publications: 13 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-57202201-C-T is Benign according to our data. Variant chr12-57202201-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

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.10595-220C>T		intron	N/A	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.10595-220C>T		intron	N/A	ENSP00000243077.3	Q07954-1
	LRP1	ENST00000555124.1	TSL:4	c.338-220C>T		intron	N/A	ENSP00000451012.1	H0YJ88

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58673 AN: 151622 Hom.: 11953 Cov.: 30

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.387 AC: 58720 AN: 151740 Hom.: 11971 Cov.: 30 AF XY: 0.384 AC XY: 28453 AN XY: 74142

African (AFR) AF: 0.516 AC: 21326 AN: 41312

American (AMR) AF: 0.335 AC: 5118 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1886 AN: 5142

South Asian (SAS) AF: 0.221 AC: 1061 AN: 4810

European-Finnish (FIN) AF: 0.404 AC: 4267 AN: 10556

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22546 AN: 67876

Other (OTH) AF: 0.370 AC: 781 AN: 2108

Alfa AF: 0.340 Hom.: 6210

Bravo AF: 0.395

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.77
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7978567; hg19: chr12-57595984; COSMIC: COSV54510743; COSMIC: COSV54510743;