1-53272511-A-G

Position:

• chr1-53272511-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.1007-1165T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,166,998 control chromosomes in the GnomAD database, including 100,279 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 0.39 (12532 hom., cov: 33)
  • Exomes 𝑓: 0.41 (87747 hom.)
• Consequence: LRP8 NM_004631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP8	NM_004631.5	c.1007-1165T>C		intron_variant		ENST00000306052.12	NP_004622.2
LRP8	NM_001018054.3	c.1007-1165T>C		intron_variant			NP_001018064.1
LRP8	NM_017522.5	c.620-1165T>C		intron_variant			NP_059992.3
LRP8	NM_033300.4	c.497-1165T>C		intron_variant			NP_150643.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052.12	c.1007-1165T>C		intron_variant		1	NM_004631.5	ENSP00000303634	A2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59656 AN: 152034 Hom.: 12526 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.408 AC: 414446 AN: 1014844 Hom.: 87747 AF XY: 0.403 AC XY: 202485 AN XY: 502800

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.777

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.392 AC: 59699 AN: 152154 Hom.: 12532 Cov.: 33 AF XY: 0.392 AC XY: 29119 AN XY: 74376

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.356

Alfa AF: 0.403 Hom.: 3834

Bravo AF: 0.385

Asia WGS AF: 0.471 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.65
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs7546246; hg19: chr1-53738183;