dbSNP rs150116835: LRP12:p.Asp839Asn (chr8-104490738-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013437.5(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
NM_013437.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.32

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

oculopharyngodistal myopathy 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen

LRP12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2658740.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 450 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013437.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP12	NM_013437.5	MANE Select	c.2515G>A	p.Asp839Asn	missense	Exon 7 of 7	NP_038465.1	Q9Y561-1
	LRP12	NM_001135703.3		c.2458G>A	p.Asp820Asn	missense	Exon 6 of 6	NP_001129175.1	Q9Y561-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRP12	ENST00000276654.10	TSL:1 MANE Select	c.2515G>A	p.Asp839Asn	missense	Exon 7 of 7	ENSP00000276654.5	Q9Y561-1
LRP12	ENST00000424843.6	TSL:2	c.2458G>A	p.Asp820Asn	missense	Exon 6 of 6	ENSP00000399148.2	Q9Y561-2
LRP12	ENST00000518375.1	TSL:2	n.1868G>A		non_coding_transcript_exon	Exon 2 of 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

GnomAD2 exomes

AF:

0.00327

AC:

820

AN:

250816

AF XY:

0.00325

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 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

African (AFR)

AF:

0.000478

AC:

AN:

33480

American (AMR)

AF:

0.00116

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000612

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000441

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00813

AC:

434

AN:

53414

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00476

AC:

5297

AN:

1111990

Other (OTH)

AF:

0.00306

AC:

185

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

351

702

1053

1404

1755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00296

AC:

450

AN:

152226

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000843

AC:

AN:

41526

American (AMR)

AF:

0.00229

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00565

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00453

AC:

308

AN:

68006

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00292

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.063

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.54

MutationAssessor

Benign

0.90

PhyloP100

7.3

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.75

REVEL

Uncertain

0.43

Sift

Uncertain

0.0040

Sift4G

Benign

0.28

Polyphen

0.99

Vest4

0.51

MVP

0.80

MPC

0.44

ClinPred

0.024

GERP RS

5.8

Varity_R

0.22

gMVP

0.54

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over