chr3-188354725-A-G

Variant names:

• chr3-188354725-A-G
• rs9865818
• NM_001375462.1:c.-10+13006A>G

Variant summary

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

The NM_001375462.1(LPP):​c.-10+13006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,174 control chromosomes in the GnomAD database, including 10,297 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 (10297 hom., cov: 33)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 25 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-10+13006A>G		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.-10+13006A>G		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52118 AN: 152056 Hom.: 10302 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.342 AC: 52117 AN: 152174 Hom.: 10297 Cov.: 33 AF XY: 0.341 AC XY: 25392 AN XY: 74394

African (AFR) AF: 0.140 AC: 5831 AN: 41554

American (AMR) AF: 0.403 AC: 6157 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1785 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5172

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4822

European-Finnish (FIN) AF: 0.353 AC: 3738 AN: 10582

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30169 AN: 67978

Other (OTH) AF: 0.380 AC: 803 AN: 2114

Alfa AF: 0.413 Hom.: 24728

Bravo AF: 0.336

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.82
DANN	Benign	0.48
PhyloP100		-0.084
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: rs9865818; hg19: chr3-188072513;