Variant rs3737983 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004631.5(LRP8):c.2622C>T(p.Asp874=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,612,428 control chromosomes in the GnomAD database, including 141,610 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 0.38 ( 11875 hom., cov: 31)

Exomes 𝑓: 0.41 ( 129735 hom. )

Consequence

LRP8
NM_004631.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.466

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=-0.466 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 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.2622C>T	p.Asp874=	synonymous_variant	17/19	ENST00000306052.12	NP_004622.2
LRP8	NM_001018054.3 linkuse as main transcript	c.2622C>T	p.Asp874=	synonymous_variant	17/18		NP_001018064.1
LRP8	NM_033300.4 linkuse as main transcript	c.2112C>T	p.Asp704=	synonymous_variant	15/17		NP_150643.2
LRP8	NM_017522.5 linkuse as main transcript	c.2010C>T	p.Asp670=	synonymous_variant	15/16		NP_059992.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP8	ENST00000306052.12 linkuse as main transcript	c.2622C>T	p.Asp874=	synonymous_variant	17/19	1	NM_004631.5	ENSP00000303634	A2	Q14114-1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57907

AN:

151788

Hom.:

11868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.403

AC:

101426

AN:

251392

Hom.:

22370

AF XY:

0.395

AC XY:

53648

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.723

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.413

AC:

603481

AN:

1460522

Hom.:

129735

Cov.:

AF XY:

0.408

AC XY:

296541

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.720

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.394

GnomAD4 genome

AF:

0.381

AC:

57947

AN:

151906

Hom.:

11875

Cov.:

AF XY:

0.381

AC XY:

28293

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.248

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.346

Alfa

AF:

0.408

Hom.:

32153

Bravo

AF:

0.373

EpiCase

AF:

0.400

EpiControl

AF:

0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.4

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over