1-53290007-A-C

Variant names:

• chr1-53290007-A-C
• rs12039021
• NM_004631.5:c.245-318T>G

Variant summary

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

The NM_004631.5(LRP8):​c.245-318T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,934 control chromosomes in the GnomAD database, including 10,421 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 0.34 (10421 hom., cov: 32)
• Consequence: LRP8 NM_004631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP8	NM_004631.5	c.245-318T>G		intron_variant	Intron 2 of 18	ENST00000306052.12	NP_004622.2
LRP8	NM_001018054.3	c.245-318T>G		intron_variant	Intron 2 of 17		NP_001018064.1
LRP8	NM_033300.4	c.245-318T>G		intron_variant	Intron 2 of 16		NP_150643.2
LRP8	NM_017522.5	c.245-318T>G		intron_variant	Intron 2 of 15		NP_059992.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052.12	c.245-318T>G		intron_variant	Intron 2 of 18	1	NM_004631.5	ENSP00000303634.6

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52354 AN: 151816 Hom.: 10412 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.345 AC: 52379 AN: 151934 Hom.: 10421 Cov.: 32 AF XY: 0.346 AC XY: 25708 AN XY: 74246

African (AFR) AF: 0.148 AC: 6147 AN: 41464

American (AMR) AF: 0.345 AC: 5264 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1445 AN: 3464

East Asian (EAS) AF: 0.593 AC: 3051 AN: 5144

South Asian (SAS) AF: 0.352 AC: 1693 AN: 4812

European-Finnish (FIN) AF: 0.455 AC: 4792 AN: 10534

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28730 AN: 67950

Other (OTH) AF: 0.344 AC: 724 AN: 2106

Alfa AF: 0.388 Hom.: 14998

Bravo AF: 0.328

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.84
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12039021; hg19: chr1-53755679;