Variant chr8-104490738-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000276654.10(LRP12):c.2515G>A(p.Asp839Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,036 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 15 hom. )

Consequence

LRP12
ENST00000276654.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.32

Variant links:

Genes affected

LRP12 (HGNC:31708): (LDL receptor related protein 12) This gene encodes a member of the low-density lipoprotein receptor related protein family. The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

LRP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01000312).

BP6

Variant 8-104490738-C-T is Benign according to our data. Variant chr8-104490738-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658740.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 450 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP12	NM_013437.5 linkuse as main transcript	c.2515G>A	p.Asp839Asn	missense_variant	7/7	ENST00000276654.10	NP_038465.1
LRP12	NM_001135703.3 linkuse as main transcript	c.2458G>A	p.Asp820Asn	missense_variant	6/6		NP_001129175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP12	ENST00000276654.10 linkuse as main transcript	c.2515G>A	p.Asp839Asn	missense_variant	7/7	1	NM_013437.5	ENSP00000276654	P4	Q9Y561-1
LRP12	ENST00000424843.6 linkuse as main transcript	c.2458G>A	p.Asp820Asn	missense_variant	6/6	2		ENSP00000399148	A1	Q9Y561-2
LRP12	ENST00000518375.1 linkuse as main transcript	n.1868G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00296

AC:

450

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00453

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00327

AC:

820

AN:

250816

Hom.:

AF XY:

0.00325

AC XY:

440

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00805

Gnomad NFE exome

AF:

0.00494

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00413

AC:

6041

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2990

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00813

Gnomad4 NFE exome

AF:

0.00476

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.00296

AC:

450

AN:

152226

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.00259

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00334

AC:

406

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

LRP12: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

0.54

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.75

N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.28

T;T

Polyphen

0.99

D;D

Vest4

0.51

MVP

0.80

MPC

0.44

ClinPred

0.024

GERP RS

5.8

Varity_R

0.22

gMVP

0.54

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

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