chr3-188524893-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001375462.1(LPP):​c.429+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 226,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000056 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

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>A		intron	N/A	NP_001362391.1	Q93052
	LPP	NM_001167671.3		c.429+106G>A		intron	N/A	NP_001161143.1	Q93052
	LPP	NM_001375455.1		c.429+106G>A		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>A		intron	N/A	ENSP00000478901.1	Q93052
	LPP	ENST00000618621.5	TSL:1	c.429+106G>A		intron	N/A	ENSP00000482617.2	Q93052
	LPP	ENST00000414139.6	TSL:4	c.429+106G>A		intron	N/A	ENSP00000392667.2	Q93052

Frequencies

GnomAD3 genomes AF: 0.0000559 AC: 1 AN: 17900 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 3 AN: 208788 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 100252

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6570

American (AMR) AF: 0.00 AC: 0 AN: 3716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2384

East Asian (EAS) AF: 0.00 AC: 0 AN: 1592

South Asian (SAS) AF: 0.00 AC: 0 AN: 7040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 704

European-Non Finnish (NFE) AF: 0.0000171 AC: 3 AN: 175440

Other (OTH) AF: 0.00 AC: 0 AN: 7936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000509044), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000559 AC: 1 AN: 17900 Hom.: 0 Cov.: 0 AF XY: 0.000117 AC XY: 1 AN XY: 8552

African (AFR) AF: 0.00 AC: 0 AN: 13744

American (AMR) AF: 0.00105 AC: 1 AN: 954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 328

East Asian (EAS) AF: 0.00 AC: 0 AN: 54

South Asian (SAS) AF: 0.00 AC: 0 AN: 194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2066

Other (OTH) AF: 0.00 AC: 0 AN: 198

Alfa AF: 0.00 Hom.: 4544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		-1.4

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;