chr3-188724692-T-C

Position:

• chr3-188724692-T-C

Variant summary

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

The NM_001375462.1(LPP):​c.1240+16299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,248 control chromosomes in the GnomAD database, including 4,488 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 0.22 (4488 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPP	NM_001375462.1	c.1240+16299T>C		intron_variant		ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.1240+16299T>C		intron_variant		1	NM_001375462.1	ENSP00000478901	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32859 AN: 152130 Hom.: 4489 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.0167

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.216 AC: 32860 AN: 152248 Hom.: 4488 Cov.: 32 AF XY: 0.213 AC XY: 15852 AN XY: 74448

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.273

Alfa AF: 0.294 Hom.: 7433

Bravo AF: 0.212

Asia WGS AF: 0.114 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.79

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: rs9290877; hg19: chr3-188442480;