rs344952

Positions:

• chr3-188180805-G-A
• chr3-188180805-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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]

FLJ42393 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-190+26553G>A		intron_variant		ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.-190+26553G>A		intron_variant		1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 65679 AN: 147078 Hom.: 16226 Cov.: 31

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: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.447 AC: 65747 AN: 147196 Hom.: 16251 Cov.: 31 AF XY: 0.449 AC XY: 32190 AN XY: 71726

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.444

Alfa AF: 0.454 Hom.: 14925

Bravo AF: 0.431

Asia WGS AF: 0.434 AC: 1504 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.60

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: rs344952; hg19: chr3-187898593; COSMIC: COSV66704092;