chr1-53301300-A-G

Variant names:

• chr1-53301300-A-G
• rs867884
• NM_004631.5:c.245-11611T>C

Variant summary

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

The NM_004631.5(LRP8):​c.245-11611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,000 control chromosomes in the GnomAD database, including 14,872 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 0.44 (14872 hom., cov: 32)
• Consequence: LRP8 NM_004631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• 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)

LOC105378726 (HGNC:):

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 = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP8	NM_004631.5	c.245-11611T>C		intron_variant	Intron 2 of 18	ENST00000306052.12	NP_004622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052.12	c.245-11611T>C		intron_variant	Intron 2 of 18	1	NM_004631.5	ENSP00000303634.6

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66030 AN: 151882 Hom.: 14831 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.435 AC: 66127 AN: 152000 Hom.: 14872 Cov.: 32 AF XY: 0.436 AC XY: 32435 AN XY: 74312

African (AFR) AF: 0.482 AC: 19967 AN: 41436

American (AMR) AF: 0.515 AC: 7867 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1535 AN: 3466

East Asian (EAS) AF: 0.682 AC: 3516 AN: 5156

South Asian (SAS) AF: 0.392 AC: 1893 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4093 AN: 10580

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25807 AN: 67942

Other (OTH) AF: 0.457 AC: 962 AN: 2106

Alfa AF: 0.404 Hom.: 37964

Bravo AF: 0.451

Asia WGS AF: 0.511 AC: 1774 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
DANN	Benign	0.42
PhyloP100		-0.43
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: rs867884; hg19: chr1-53766972;