rs7645635

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001375462.1(LPP):c.1036T>C(p.Tyr346His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,912 control chromosomes in the GnomAD database, including 14,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 7521 hom., cov: 32)

Exomes 𝑓: 0.019 ( 6777 hom. )

Consequence

LPP
NM_001375462.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.23

Publications

13 publications found

Variant links:

Genes affected

LPP (HGNC:6679): (LIM domain containing preferred translocation partner in lipoma) This gene encodes a member of a subfamily of LIM domain proteins that are characterized by an N-terminal proline-rich region and three C-terminal LIM domains. The encoded protein localizes to the cell periphery in focal adhesions and may be involved in cell-cell adhesion and cell motility. This protein also shuttles through the nucleus and may function as a transcriptional co-activator. This gene is located at the junction of certain disease-related chromosomal translocations, which result in the expression of chimeric proteins that may promote tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

LPP links:

ENSG00000295499 (HGNC:):

ENSG00000295499 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.5052405E-5).

BP6

Variant 3-188609767-T-C is Benign according to our data. Variant chr3-188609767-T-C is described in ClinVar as Benign. ClinVar VariationId is 1256811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LPP	NM_001375462.1	MANE Select	c.1036T>C	p.Tyr346His	missense	Exon 7 of 12	NP_001362391.1
LPP	NM_001167671.3		c.1036T>C	p.Tyr346His	missense	Exon 7 of 12	NP_001161143.1
LPP	NM_001375455.1		c.1036T>C	p.Tyr346His	missense	Exon 6 of 11	NP_001362384.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LPP	ENST00000617246.5	TSL:1 MANE Select	c.1036T>C	p.Tyr346His	missense	Exon 7 of 12	ENSP00000478901.1
LPP	ENST00000618621.5	TSL:1	c.1036T>C	p.Tyr346His	missense	Exon 6 of 11	ENSP00000482617.2
LPP	ENST00000414139.6	TSL:4	c.1036T>C	p.Tyr346His	missense	Exon 6 of 11	ENSP00000392667.2

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26387

AN:

151982

Hom.:

7500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.0469

AC:

11685

AN:

249002

AF XY:

0.0351

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.0336

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00322

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0193

AC:

28261

AN:

1461812

Hom.:

6777

Cov.:

AF XY:

0.0169

AC XY:

12301

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.616

AC:

20620

AN:

33478

American (AMR)

AF:

0.0377

AC:

1685

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

289

AN:

26130

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39690

South Asian (SAS)

AF:

0.00399

AC:

344

AN:

86258

European-Finnish (FIN)

AF:

0.00103

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.0482

AC:

278

AN:

5762

European-Non Finnish (NFE)

AF:

0.00223

AC:

2477

AN:

1111992

Other (OTH)

AF:

0.0416

AC:

2510

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

890

1780

2669

3559

4449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.174

AC:

26449

AN:

152100

Hom.:

7521

Cov.:

AF XY:

0.166

AC XY:

12384

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.597

AC:

24737

AN:

41402

American (AMR)

AF:

0.0748

AC:

1143

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00350

AC:

238

AN:

68014

Other (OTH)

AF:

0.125

AC:

262

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

569

1138

1707

2276

2845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0688

Hom.:

5721

Bravo

AF:

0.199

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.586

AC:

2581

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.0568

AC:

6900

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00528

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.80

MetaRNN

Benign

0.000075

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

PhyloP100

7.2

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Uncertain

0.0050

Sift4G

Benign

0.41

Polyphen

1.0

Vest4

0.85

ClinPred

0.038

GERP RS

6.2

Varity_R

0.081

gMVP

0.55

Mutation Taster

=95/5

polymorphism (auto)

(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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over