rs12634152

Variant names:

• chr3-188403231-C-T
• rs12634152
• NM_001375462.1:c.-9-2881C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375462.1(LPP):​c.-9-2881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,870 control chromosomes in the GnomAD database, including 15,757 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 0.43 (15757 hom., cov: 31)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-9-2881C>T		intron_variant	Intron 3 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.-9-2881C>T		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65998 AN: 151752 Hom.: 15762 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.435 AC: 66009 AN: 151870 Hom.: 15757 Cov.: 31 AF XY: 0.431 AC XY: 31968 AN XY: 74242

African (AFR) AF: 0.239 AC: 9890 AN: 41342

American (AMR) AF: 0.467 AC: 7135 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1873 AN: 5150

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4820

European-Finnish (FIN) AF: 0.432 AC: 4560 AN: 10544

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37158 AN: 67954

Other (OTH) AF: 0.455 AC: 962 AN: 2112

Alfa AF: 0.489 Hom.: 2350

Bravo AF: 0.429

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.73
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12634152; hg19: chr3-188121019;