1-53246063-G-C

Position:

• chr1-53246063-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004631.5(LRP8):​c.*955C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,030 control chromosomes in the GnomAD database, including 9,149 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 0.32 (9148 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: LRP8 NM_004631.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP8	NM_004631.5	c.*955C>G		3_prime_UTR_variant	19/19	ENST00000306052.12	NP_004622.2
LRP8	NM_001018054.3	c.*955C>G		3_prime_UTR_variant	18/18		NP_001018064.1
LRP8	NM_033300.4	c.*955C>G		3_prime_UTR_variant	17/17		NP_150643.2
LRP8	NM_017522.5	c.*955C>G		3_prime_UTR_variant	16/16		NP_059992.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052	c.*955C>G		3_prime_UTR_variant	19/19	1	NM_004631.5	ENSP00000303634.6

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48279 AN: 151902 Hom.: 9143 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.318 AC: 48289 AN: 152020 Hom.: 9148 Cov.: 32 AF XY: 0.317 AC XY: 23547 AN XY: 74296

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.300

Alfa AF: 0.251 Hom.: 758

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
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: rs5177; hg19: chr1-53711735;