rs60946162

Variant names:

• chr3-188415548-C-T
• rs60946162
• NM_001375462.1:c.193+9235C>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.193+9235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,606 control chromosomes in the GnomAD database, including 10,970 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 0.35 (10970 hom., cov: 31)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPP	NM_001375462.1	MANE Select	c.193+9235C>T		intron	N/A	NP_001362391.1
	LPP	NM_001167671.3		c.193+9235C>T		intron	N/A	NP_001161143.1
	LPP	NM_001375455.1		c.193+9235C>T		intron	N/A	NP_001362384.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPP	ENST00000617246.5	TSL:1 MANE Select	c.193+9235C>T		intron	N/A	ENSP00000478901.1
	LPP	ENST00000618621.5	TSL:1	c.193+9235C>T		intron	N/A	ENSP00000482617.2
	LPP	ENST00000414139.6	TSL:4	c.193+9235C>T		intron	N/A	ENSP00000392667.2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52763 AN: 151488 Hom.: 10977 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.348 AC: 52748 AN: 151606 Hom.: 10970 Cov.: 31 AF XY: 0.346 AC XY: 25591 AN XY: 74056

African (AFR) AF: 0.113 AC: 4659 AN: 41318

American (AMR) AF: 0.415 AC: 6308 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1718 AN: 3460

East Asian (EAS) AF: 0.319 AC: 1646 AN: 5162

South Asian (SAS) AF: 0.301 AC: 1445 AN: 4802

European-Finnish (FIN) AF: 0.384 AC: 4017 AN: 10472

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31430 AN: 67880

Other (OTH) AF: 0.393 AC: 825 AN: 2100

Alfa AF: 0.418 Hom.: 3023

Bravo AF: 0.341

Asia WGS AF: 0.281 AC: 978 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.71
PhyloP100		0.13
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: rs60946162; hg19: chr3-188133336;