3-188524893-G-T

Variant names:

• chr3-188524893-G-T
• rs56275744
• NM_001375462.1:c.429+106G>T

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+106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 215,504 control chromosomes in the GnomAD database, including 52,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (598 hom., cov: 0)
  • Exomes 𝑓: 0.68 (51557 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 1 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=-1.04).
• BP6: Variant 3-188524893-G-T is Benign according to our data. Variant chr3-188524893-G-T is described in ClinVar as Benign. ClinVar VariationId is 1246296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 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+106G>T		intron	N/A	NP_001362391.1	Q93052
	LPP	NM_001167671.3		c.429+106G>T		intron	N/A	NP_001161143.1	Q93052
	LPP	NM_001375455.1		c.429+106G>T		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+106G>T		intron	N/A	ENSP00000478901.1	Q93052
	LPP	ENST00000618621.5	TSL:1	c.429+106G>T		intron	N/A	ENSP00000482617.2	Q93052
	LPP	ENST00000414139.6	TSL:4	c.429+106G>T		intron	N/A	ENSP00000392667.2	Q93052

Frequencies

GnomAD3 genomes AF: 0.395 AC: 6884 AN: 17412 Hom.: 596 Cov.: 0

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.684 AC: 135467 AN: 198064 Hom.: 51557 AF XY: 0.676 AC XY: 64152 AN XY: 94964

African (AFR) AF: 0.481 AC: 2995 AN: 6228

American (AMR) AF: 0.431 AC: 1537 AN: 3570

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1212 AN: 2260

East Asian (EAS) AF: 0.783 AC: 1035 AN: 1322

South Asian (SAS) AF: 0.494 AC: 3319 AN: 6714

European-Finnish (FIN) AF: 0.313 AC: 1010 AN: 3226

Middle Eastern (MID) AF: 0.479 AC: 322 AN: 672

European-Non Finnish (NFE) AF: 0.716 AC: 119265 AN: 166556

Other (OTH) AF: 0.635 AC: 4772 AN: 7516

GnomAD4 genome AF: 0.396 AC: 6900 AN: 17440 Hom.: 598 Cov.: 0 AF XY: 0.394 AC XY: 3301 AN XY: 8368

African (AFR) AF: 0.467 AC: 6238 AN: 13370

American (AMR) AF: 0.289 AC: 268 AN: 928

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 104 AN: 324

East Asian (EAS) AF: 0.260 AC: 13 AN: 50

South Asian (SAS) AF: 0.106 AC: 20 AN: 188

European-Finnish (FIN) AF: 0.0512 AC: 13 AN: 254

Middle Eastern (MID) AF: 0.182 AC: 4 AN: 22

European-Non Finnish (NFE) AF: 0.0851 AC: 173 AN: 2032

Other (OTH) AF: 0.332 AC: 65 AN: 196

Alfa AF: 0.721 Hom.: 4544

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	-1.0
CADD	Benign	0.77
DANN	Benign	0.30
PhyloP100		-1.4
Mutation Taster		=18/82	disease causing (long InDel)

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: rs56275744; hg19: chr3-188242681; COSMIC: COSV57078778; COSMIC: COSV57078778;