rs2788032

Positions:

• chr1-53311959-A-C
• chr1-53311959-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.244+14914T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,142 control chromosomes in the GnomAD database, including 2,570 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 0.16 (2570 hom., cov: 33)
• Consequence: LRP8 NM_004631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP8	NM_004631.5	c.244+14914T>G		intron_variant		ENST00000306052.12
LRP8	NM_001018054.3	c.244+14914T>G		intron_variant
LRP8	NM_017522.5	c.244+14914T>G		intron_variant
LRP8	NM_033300.4	c.244+14914T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP8	ENST00000306052.12	c.244+14914T>G		intron_variant		1	NM_004631.5	A2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23648 AN: 152024 Hom.: 2561 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.156 AC: 23699 AN: 152142 Hom.: 2570 Cov.: 33 AF XY: 0.155 AC XY: 11556 AN XY: 74362

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0953 Hom.: 718

Bravo AF: 0.158

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
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: rs2788032; hg19: chr1-53777631; COSMIC: COSV60097130; COSMIC: COSV60097130;