rs6444284

Variant names:

• chr3-188399529-C-T
• rs6444284
• NM_001375462.1:c.-9-6583C>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.-9-6583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,072 control chromosomes in the GnomAD database, including 29,632 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 0.62 (29632 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-9-6583C>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.-9-6583C>T		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94115 AN: 151954 Hom.: 29622 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.619 AC: 94165 AN: 152072 Hom.: 29632 Cov.: 32 AF XY: 0.613 AC XY: 45546 AN XY: 74326

African (AFR) AF: 0.739 AC: 30669 AN: 41486

American (AMR) AF: 0.556 AC: 8492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2140 AN: 3468

East Asian (EAS) AF: 0.567 AC: 2930 AN: 5172

South Asian (SAS) AF: 0.432 AC: 2081 AN: 4820

European-Finnish (FIN) AF: 0.520 AC: 5488 AN: 10556

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.593 AC: 40307 AN: 67974

Other (OTH) AF: 0.592 AC: 1247 AN: 2108

Alfa AF: 0.616 Hom.: 6032

Bravo AF: 0.631

Asia WGS AF: 0.523 AC: 1820 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	3.2
DANN	Benign	0.60
PhyloP100		0.013
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: rs6444284; hg19: chr3-188117317;