Genetic Variant LPP:c.-190+26553G>A (chr3-188180805-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375462.1(LPP):c.-190+26553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 147,202 control chromosomes in the GnomAD database, including 16,252 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16251 hom., cov: 31)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

LPP
NM_001375462.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.332

Publications

5 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:

FLJ42393 (HGNC:):

FLJ42393 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 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	Effect	Exon Rank	Protein	UniProt
LPP	NM_001375462.1	MANE Select	c.-190+26553G>A	intron	N/A	NP_001362391.1	Q93052
LPP	NM_001167671.3		c.-190+26784G>A	intron	N/A	NP_001161143.1	Q93052
LPP	NM_001375455.1		c.-133+27442G>A	intron	N/A	NP_001362384.1	Q93052

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPP	ENST00000617246.5	TSL:1 MANE Select	c.-190+26553G>A	intron	N/A	ENSP00000478901.1	Q93052
LPP	ENST00000414139.6	TSL:4	c.-133+26784G>A	intron	N/A	ENSP00000392667.2	Q93052
LPP	ENST00000854486.1		c.-251-27395G>A	intron	N/A	ENSP00000524545.1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

65679

AN:

147078

Hom.:

16226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.439

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.447

AC:

65747

AN:

147196

Hom.:

16251

Cov.:

AF XY:

0.449

AC XY:

32190

AN XY:

71726

show subpopulations

African (AFR)

AF:

0.366

AC:

15056

AN:

41146

American (AMR)

AF:

0.461

AC:

6516

AN:

14138

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

1436

AN:

3348

East Asian (EAS)

AF:

0.455

AC:

2055

AN:

4520

South Asian (SAS)

AF:

0.288

AC:

1281

AN:

4442

European-Finnish (FIN)

AF:

0.578

AC:

5904

AN:

10208

Middle Eastern (MID)

AF:

0.414

AC:

115

AN:

278

European-Non Finnish (NFE)

AF:

0.484

AC:

32017

AN:

66210

Other (OTH)

AF:

0.444

AC:

892

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

1541

3083

4624

6166

7707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.447

Hom.:

25409

Bravo

AF:

0.431

Asia WGS

AF:

0.434

AC:

1504

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

(source)

DANN

Benign

0.60

PhyloP100

-0.33

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over