1-53310944-C-T

Variant names:

• chr1-53310944-C-T
• rs1288480
• NM_004631.5:c.244+15929G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004631.5(LRP8):​c.244+15929G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,010 control chromosomes in the GnomAD database, including 14,241 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 0.42 (14241 hom., cov: 32)
• Consequence: LRP8 NM_004631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• Publications: 4 publications found

Genes affected

LRP8 (HGNC:6700): (LDL receptor related protein 8) This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]

LRP8 Gene-Disease associations (from GenCC):

• Tourette syndrome

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004631.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP8	NM_004631.5	MANE Select	c.244+15929G>A		intron	N/A	NP_004622.2
	LRP8	NM_001018054.3		c.244+15929G>A		intron	N/A	NP_001018064.1
	LRP8	NM_033300.4		c.244+15929G>A		intron	N/A	NP_150643.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP8	ENST00000306052.12	TSL:1 MANE Select	c.244+15929G>A		intron	N/A	ENSP00000303634.6
	LRP8	ENST00000371454.6	TSL:1	c.244+15929G>A		intron	N/A	ENSP00000360509.2
	LRP8	ENST00000347547.7	TSL:1	c.244+15929G>A		intron	N/A	ENSP00000334522.2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63400 AN: 151892 Hom.: 14193 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.418 AC: 63511 AN: 152010 Hom.: 14241 Cov.: 32 AF XY: 0.417 AC XY: 30956 AN XY: 74304

African (AFR) AF: 0.530 AC: 21968 AN: 41440

American (AMR) AF: 0.496 AC: 7585 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3472

East Asian (EAS) AF: 0.687 AC: 3543 AN: 5156

South Asian (SAS) AF: 0.382 AC: 1840 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2766 AN: 10578

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23004 AN: 67942

Other (OTH) AF: 0.435 AC: 919 AN: 2112

Alfa AF: 0.354 Hom.: 7757

Bravo AF: 0.445

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.096
DANN	Benign	0.73
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1288480; hg19: chr1-53776616;