Genetic Variant LPP:c.429+122T>G (chr3-188524909-T-G) – ACMG Classification: Benign (-20 pts)

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.429+122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 8493 hom., cov: 20)

Exomes 𝑓: 0.29 ( 15344 hom. )

Failed GnomAD Quality Control

Consequence

LPP
NM_001375462.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.215

Publications

1 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:

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 (BayesDel_noAF=-0.92).

BP6

Variant 3-188524909-T-G is Benign according to our data. Variant chr3-188524909-T-G is described in ClinVar as [Benign]. Clinvar id is 1271654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1 link	c.429+122T>G		intron_variant	Intron 6 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5 link	c.429+122T>G		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1		Q93052

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

46483

AN:

132488

Hom.:

8493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.366

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.286

AC:

95580

AN:

334708

Hom.:

15344

AF XY:

0.287

AC XY:

50410

AN XY:

175602

show subpopulations

African (AFR)

AF:

0.391

AC:

2960

AN:

7562

American (AMR)

AF:

0.217

AC:

2535

AN:

11702

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

3275

AN:

10040

East Asian (EAS)

AF:

0.0426

AC:

1068

AN:

25074

South Asian (SAS)

AF:

0.272

AC:

5978

AN:

21994

European-Finnish (FIN)

AF:

0.348

AC:

9666

AN:

27770

Middle Eastern (MID)

AF:

0.358

AC:

609

AN:

1702

European-Non Finnish (NFE)

AF:

0.304

AC:

63550

AN:

209360

Other (OTH)

AF:

0.305

AC:

5939

AN:

19504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

2568

5136

7703

10271

12839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.351

AC:

46508

AN:

132536

Hom.:

8493

Cov.:

AF XY:

0.344

AC XY:

21833

AN XY:

63462

show subpopulations

African (AFR)

AF:

0.401

AC:

13708

AN:

34182

American (AMR)

AF:

0.312

AC:

4030

AN:

12914

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1165

AN:

3296

East Asian (EAS)

AF:

0.0331

AC:

156

AN:

4710

South Asian (SAS)

AF:

0.309

AC:

1173

AN:

3790

European-Finnish (FIN)

AF:

0.333

AC:

2492

AN:

7478

Middle Eastern (MID)

AF:

0.401

AC:

105

AN:

262

European-Non Finnish (NFE)

AF:

0.358

AC:

22647

AN:

63228

Other (OTH)

AF:

0.367

AC:

666

AN:

1816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

1160

2320

3479

4639

5799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.7

(source)

DANN

Benign

0.42

PhyloP100

-0.21

Mutation Taster

=100/0

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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3-188524909-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over