1-53301300-A-G

Position:

• chr1-53301300-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LRP8	NM_004631.5	c.245-11611T>C		intron_variant		ENST00000306052.12	NP_004622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052.12	c.245-11611T>C		intron_variant		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

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.457

Alfa AF: 0.393 Hom.: 19824

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs867884; hg19: chr1-53766972;