Variant chr1-53247055-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004631.5(LRP8):c.2855G>A(p.Arg952Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.356 in 1,591,796 control chromosomes in the GnomAD database, including 112,067 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.28 ( 7722 hom., cov: 32)

Exomes 𝑓: 0.36 ( 104345 hom. )

Consequence

LRP8
NM_004631.5 missense, splice_region

Scores

Splicing: ADA: 0.9742

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 7.18

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP8	NM_004631.5 linkuse as main transcript	c.2855G>A	p.Arg952Gln	missense_variant, splice_region_variant	19/19	ENST00000306052.12	NP_004622.2
LRP8	NM_001018054.3 linkuse as main transcript	c.2678G>A	p.Arg893Gln	missense_variant, splice_region_variant	18/18		NP_001018064.1
LRP8	NM_033300.4 linkuse as main transcript	c.2345G>A	p.Arg782Gln	missense_variant, splice_region_variant	17/17		NP_150643.2
LRP8	NM_017522.5 linkuse as main transcript	c.2066G>A	p.Arg689Gln	missense_variant, splice_region_variant	16/16		NP_059992.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052.12 linkuse as main transcript	c.2855G>A	p.Arg952Gln	missense_variant, splice_region_variant	19/19	1	NM_004631.5	ENSP00000303634	A2	Q14114-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42102

AN:

151976

Hom.:

7720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0721

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.0328

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.292

AC:

66973

AN:

229590

Hom.:

12149

AF XY:

0.296

AC XY:

36888

AN XY:

124524

show subpopulations

Gnomad AFR exome

AF:

0.0647

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.0310

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.365

AC:

524945

AN:

1439702

Hom.:

104345

Cov.:

AF XY:

0.361

AC XY:

258129

AN XY:

715976

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.0396

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.408

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.277

AC:

42103

AN:

152094

Hom.:

7722

Cov.:

AF XY:

0.274

AC XY:

20355

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.0330

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.363

Hom.:

25639

Bravo

AF:

0.253

TwinsUK

AF:

0.402

AC:

1490

ALSPAC

AF:

0.411

AC:

1584

ESP6500AA

AF:

0.0828

AC:

365

ESP6500EA

AF:

0.395

AC:

3401

ExAC

AF:

0.294

AC:

35749

Asia WGS

AF:

0.121

AC:

424

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myocardial infarction, susceptibility to, 1

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Oct 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.049

T;.;.;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;T;.;T;D

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.69

N;.;.;.;.

MutationTaster

Benign

0.0000025

P;P;P;P;P

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.29

N;N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.049

D;T;T;T;D

Sift4G

Pathogenic

0.0

D;T;T;T;D

Polyphen

1.0

D;P;D;D;D

Vest4

0.45

MPC

1.2

ClinPred

0.033

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.82

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over