3-188419979-A-G

Position:

• chr3-188419979-A-G

Variant summary

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

The NM_001375462.1(LPP):​c.193+13666A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,190 control chromosomes in the GnomAD database, including 4,054 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 0.23 (4054 hom., cov: 33)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPP	NM_001375462.1	c.193+13666A>G		intron_variant		ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.193+13666A>G		intron_variant		1	NM_001375462.1	ENSP00000478901	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34293 AN: 152072 Hom.: 4044 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.226 AC: 34341 AN: 152190 Hom.: 4054 Cov.: 33 AF XY: 0.227 AC XY: 16914 AN XY: 74394

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.221

Alfa AF: 0.223 Hom.: 459

Bravo AF: 0.215

Asia WGS AF: 0.199 AC: 686 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.52

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: rs13319297; hg19: chr3-188137767;