rs1288499

Variant names:

• chr1-53292263-G-A
• rs1288499
• NM_004631.5:c.245-2574C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-53292263-G-A
• chr1-53292263-G-C
• chr1-53292263-G-T

Variant summary

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

The NM_004631.5(LRP8):​c.245-2574C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,278 control chromosomes in the GnomAD database, including 595 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 0.057 (595 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: LRP8 NM_004631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP8	NM_004631.5	c.245-2574C>T		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.245-2574C>T		intron_variant	Intron 2 of 18	1	NM_004631.5	ENSP00000303634.6

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8605 AN: 152160 Hom.: 587 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0358

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

GnomAD4 genome AF: 0.0567 AC: 8636 AN: 152278 Hom.: 595 Cov.: 33 AF XY: 0.0553 AC XY: 4121 AN XY: 74464

African (AFR) AF: 0.166 AC: 6875 AN: 41524

American (AMR) AF: 0.0236 AC: 361 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5188

South Asian (SAS) AF: 0.0556 AC: 269 AN: 4834

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 735 AN: 68032

Other (OTH) AF: 0.0354 AC: 75 AN: 2116

Alfa AF: 0.0313 Hom.: 453

Bravo AF: 0.0609

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.59
PhyloP100		-0.077
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: rs1288499; hg19: chr1-53757935;