Genetic Variant LRP12:p.Arg828Cys (chr8-104490771-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_013437.5(LRP12):c.2482C>T(p.Arg828Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000529 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

LRP12
NM_013437.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03566128).

BP6

Variant 8-104490771-G-A is Benign according to our data. Variant chr8-104490771-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658741.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP12	NM_013437.5 link	c.2482C>T	p.Arg828Cys	missense_variant	Exon 7 of 7	ENST00000276654.10	NP_038465.1	Q9Y561-1Q59H02
LRP12	NM_001135703.3 link	c.2425C>T	p.Arg809Cys	missense_variant	Exon 6 of 6		NP_001129175.1	Q9Y561-2Q59H02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP12	ENST00000276654.10 link	c.2482C>T	p.Arg828Cys	missense_variant	Exon 7 of 7	1	NM_013437.5	ENSP00000276654.5	Q9Y561-1
LRP12	ENST00000424843.6 link	c.2425C>T	p.Arg809Cys	missense_variant	Exon 6 of 6	2		ENSP00000399148.2	Q9Y561-2
LRP12	ENST00000518375.1 link	n.1835C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000326

AC:

AN:

251330

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000549

AC:

803

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

381

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000688

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000335

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000678

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LRP12: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.20

.;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.23

Sift

Benign

0.084

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0070

B;B

Vest4

0.18

MVP

0.40

MPC

0.32

ClinPred

0.023

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.19

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