rs2049218

chr3-188405190-C-T

Variant summary

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

The NM_001375462.1(LPP):c.-9-922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,120 control chromosomes in the GnomAD database, including 10,634 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 0.34 (10634 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.-9-922C>T		intron_variant		ENST00000617246.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.-9-922C>T		intron_variant		1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52245 AN: 152002 Hom.: 10642 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.343 AC: 52232 AN: 152120 Hom.: 10634 Cov.: 32 AF XY: 0.341 AC XY: 25343 AN XY: 74344

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.380

Alfa AF: 0.367 Hom.: 2139

Bravo AF: 0.338

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.7
Dann	Benign	0.48

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: rs2049218; hg19: chr3-188122978;