3-188524917-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001375462.1(LPP):c.429+130T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 636,882 control chromosomes in the GnomAD database, including 109,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14182 hom., cov: 24)
  • Exomes 𝑓: 0.58 (95578 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.897

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-188524917-T-G is Benign according to our data. Variant chr3-188524917-T-G is described in ClinVar as [Benign]. Clinvar id is 1275168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.429+130T>G		intron_variant		ENST00000617246.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.429+130T>G		intron_variant		1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 59110 AN: 145494 Hom.: 14190 Cov.: 24

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.578 AC: 283871 AN: 491312 Hom.: 95578 AF XY: 0.569 AC XY: 143944 AN XY: 253116

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.899

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.406 AC: 59105 AN: 145570 Hom.: 14182 Cov.: 24 AF XY: 0.405 AC XY: 28414 AN XY: 70240

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.407

Alfa AF: 0.223 Hom.: 511

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.6
Dann	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs144299808; hg19: chr3-188242705; COSMIC: COSV57090842; COSMIC: COSV57090842;