Genetic Variant LPP:c.429+118T>G (chr3-188524905-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+118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 246,186 control chromosomes in the GnomAD database, including 1,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1373 hom., cov: 19)

Exomes 𝑓: 0.076 ( 441 hom. )

Consequence

LPP
NM_001375462.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.342

Publications

0 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:

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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=-0.94).

BP6

Variant 3-188524905-T-G is Benign according to our data. Variant chr3-188524905-T-G is described in ClinVar as [Benign]. Clinvar id is 1224088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1 link	c.429+118T>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+118T>G		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1		Q93052

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

12764

AN:

105476

Hom.:

1369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0538

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.00255

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0612

Gnomad MID

AF:

0.0613

Gnomad NFE

AF:

0.0362

Gnomad OTH

AF:

0.0951

GnomAD4 exome

AF:

0.0761

AC:

10698

AN:

140638

Hom.:

441

AF XY:

0.0735

AC XY:

5331

AN XY:

72524

show subpopulations

African (AFR)

AF:

0.403

AC:

1898

AN:

4704

American (AMR)

AF:

0.0671

AC:

322

AN:

4802

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

920

AN:

4574

East Asian (EAS)

AF:

0.00502

AC:

107

AN:

21316

South Asian (SAS)

AF:

0.0431

AC:

360

AN:

8360

European-Finnish (FIN)

AF:

0.140

AC:

1287

AN:

9202

Middle Eastern (MID)

AF:

0.121

AC:

AN:

580

European-Non Finnish (NFE)

AF:

0.0604

AC:

4781

AN:

79138

Other (OTH)

AF:

0.120

AC:

953

AN:

7962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

396

791

1187

1582

1978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.121

AC:

12786

AN:

105548

Hom.:

1373

Cov.:

AF XY:

0.122

AC XY:

6154

AN XY:

50632

show subpopulations

African (AFR)

AF:

0.330

AC:

9487

AN:

28722

American (AMR)

AF:

0.0537

AC:

540

AN:

10062

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

336

AN:

2564

East Asian (EAS)

AF:

0.00256

AC:

AN:

4290

South Asian (SAS)

AF:

0.0210

AC:

AN:

3052

European-Finnish (FIN)

AF:

0.0612

AC:

374

AN:

6116

Middle Eastern (MID)

AF:

0.0686

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.0362

AC:

1759

AN:

48568

Other (OTH)

AF:

0.0941

AC:

137

AN:

1456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

392

784

1175

1567

1959

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 20, 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

-0.94

CADD

Benign

1.5

(source)

DANN

Benign

0.30

PhyloP100

-0.34

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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3-188524905-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