chr3-188365131-T-C

Variant names:

• chr3-188365131-T-C
• rs4686953
• NM_001375462.1:c.-10+23412T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375462.1(LPP):​c.-10+23412T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 147,392 control chromosomes in the GnomAD database, including 10,211 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 (10211 hom., cov: 28)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 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.-10+23412T>C		intron	N/A	NP_001362391.1	Q93052
	LPP	NM_001167671.3		c.-10+23412T>C		intron	N/A	NP_001161143.1	Q93052
	LPP	NM_001375455.1		c.-9-40981T>C		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.-10+23412T>C		intron	N/A	ENSP00000478901.1	Q93052
	LPP	ENST00000618621.5	TSL:1	c.-9-40981T>C		intron	N/A	ENSP00000482617.2	Q93052
	LPP	ENST00000414139.6	TSL:4	c.-9-40981T>C		intron	N/A	ENSP00000392667.2	Q93052

Frequencies

GnomAD3 genomes AF: 0.348 AC: 51209 AN: 147294 Hom.: 10218 Cov.: 28

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.610

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.347 AC: 51202 AN: 147392 Hom.: 10211 Cov.: 28 AF XY: 0.345 AC XY: 24731 AN XY: 71742

African (AFR) AF: 0.134 AC: 5424 AN: 40404

American (AMR) AF: 0.409 AC: 6027 AN: 14734

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1576 AN: 3412

East Asian (EAS) AF: 0.297 AC: 1434 AN: 4830

South Asian (SAS) AF: 0.303 AC: 1392 AN: 4592

European-Finnish (FIN) AF: 0.354 AC: 3340 AN: 9438

Middle Eastern (MID) AF: 0.590 AC: 170 AN: 288

European-Non Finnish (NFE) AF: 0.458 AC: 30542 AN: 66752

Other (OTH) AF: 0.384 AC: 782 AN: 2038

Alfa AF: 0.411 Hom.: 3012

Bravo AF: 0.336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.067
DANN	Benign	0.47
PhyloP100		-1.1
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: rs4686953; hg19: chr3-188082919; COSMIC: COSV57108916;