Genetic Variant NM_001375462.1:c.429+106G>T (chr3-188524893-G-T) – 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+106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 215,504 control chromosomes in the GnomAD database, including 52,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 598 hom., cov: 0)

Exomes 𝑓: 0.68 ( 51557 hom. )

Consequence

LPP
NM_001375462.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.35

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:

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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=-1.04).

BP6

Variant 3-188524893-G-T is Benign according to our data. Variant chr3-188524893-G-T is described in ClinVar as [Benign]. Clinvar id is 1246296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1 link	c.429+106G>T		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+106G>T		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1		Q93052

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

6884

AN:

17412

Hom.:

596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0512

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.0855

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.684

AC:

135467

AN:

198064

Hom.:

51557

AF XY:

0.676

AC XY:

64152

AN XY:

94964

show subpopulations

African (AFR)

AF:

0.481

AC:

2995

AN:

6228

American (AMR)

AF:

0.431

AC:

1537

AN:

3570

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1212

AN:

2260

East Asian (EAS)

AF:

0.783

AC:

1035

AN:

1322

South Asian (SAS)

AF:

0.494

AC:

3319

AN:

6714

European-Finnish (FIN)

AF:

0.313

AC:

1010

AN:

3226

Middle Eastern (MID)

AF:

0.479

AC:

322

AN:

672

European-Non Finnish (NFE)

AF:

0.716

AC:

119265

AN:

166556

Other (OTH)

AF:

0.635

AC:

4772

AN:

7516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

1358

2717

4075

5434

6792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.396

AC:

6900

AN:

17440

Hom.:

598

Cov.:

AF XY:

0.394

AC XY:

3301

AN XY:

8368

show subpopulations

African (AFR)

AF:

0.467

AC:

6238

AN:

13370

American (AMR)

AF:

0.289

AC:

268

AN:

928

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

104

AN:

324

East Asian (EAS)

AF:

0.260

AC:

AN:

South Asian (SAS)

AF:

0.106

AC:

AN:

188

European-Finnish (FIN)

AF:

0.0512

AC:

AN:

254

Middle Eastern (MID)

AF:

0.182

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0851

AC:

173

AN:

2032

Other (OTH)

AF:

0.332

AC:

AN:

196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

213

426

638

851

1064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.721

Hom.:

4544

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

-1.0

CADD

Benign

0.77

(source)

DANN

Benign

0.30

PhyloP100

-1.4

Mutation Taster

=18/82

disease causing (long InDel)

(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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NM_001375462.1:c.429+106G>T

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