3-188524917-T-G

Variant names:

• chr3-188524917-T-G
• rs144299808
• NM_001375462.1:c.429+130T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375462.1(LPP):​c.429+130T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 636,882 control chromosomes in the GnomAD database, including 109,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14182 hom., cov: 24)
  • Exomes 𝑓: 0.58 (95578 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.897
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-188524917-T-G is Benign according to our data. Variant chr3-188524917-T-G is described in ClinVar as Benign. ClinVar VariationId is 1275168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPP	NM_001375462.1	MANE Select	c.429+130T>G		intron	N/A	NP_001362391.1	Q93052
	LPP	NM_001167671.3		c.429+130T>G		intron	N/A	NP_001161143.1	Q93052
	LPP	NM_001375455.1		c.429+130T>G		intron	N/A	NP_001362384.1	Q93052

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPP	ENST00000617246.5	TSL:1 MANE Select	c.429+130T>G		intron	N/A	ENSP00000478901.1	Q93052
	LPP	ENST00000618621.5	TSL:1	c.429+130T>G		intron	N/A	ENSP00000482617.2	Q93052
	LPP	ENST00000414139.6	TSL:4	c.429+130T>G		intron	N/A	ENSP00000392667.2	Q93052

Frequencies

GnomAD3 genomes AF: 0.406 AC: 59110 AN: 145494 Hom.: 14190 Cov.: 24

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.578 AC: 283871 AN: 491312 Hom.: 95578 AF XY: 0.569 AC XY: 143944 AN XY: 253116

African (AFR) AF: 0.225 AC: 2276 AN: 10106

American (AMR) AF: 0.543 AC: 7803 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 5533 AN: 11782

East Asian (EAS) AF: 0.899 AC: 24600 AN: 27370

South Asian (SAS) AF: 0.468 AC: 14638 AN: 31276

European-Finnish (FIN) AF: 0.455 AC: 14332 AN: 31484

Middle Eastern (MID) AF: 0.402 AC: 885 AN: 2204

European-Non Finnish (NFE) AF: 0.594 AC: 200395 AN: 337408

Other (OTH) AF: 0.530 AC: 13409 AN: 25320

GnomAD4 genome AF: 0.406 AC: 59105 AN: 145570 Hom.: 14182 Cov.: 24 AF XY: 0.405 AC XY: 28414 AN XY: 70240

African (AFR) AF: 0.204 AC: 8071 AN: 39586

American (AMR) AF: 0.462 AC: 6636 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1503 AN: 3426

East Asian (EAS) AF: 0.904 AC: 4498 AN: 4974

South Asian (SAS) AF: 0.467 AC: 2086 AN: 4468

European-Finnish (FIN) AF: 0.388 AC: 3495 AN: 9002

Middle Eastern (MID) AF: 0.360 AC: 103 AN: 286

European-Non Finnish (NFE) AF: 0.475 AC: 31649 AN: 66574

Other (OTH) AF: 0.407 AC: 812 AN: 1996

Alfa AF: 0.223 Hom.: 511

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.90
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: rs144299808; hg19: chr3-188242705; COSMIC: COSV57090842; COSMIC: COSV57090842;