3-188366199-C-T

Variant names:

• chr3-188366199-C-T
• rs76211316
• NM_001375462.1:c.-10+24480C>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.-10+24480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 152,292 control chromosomes in the GnomAD database, including 150 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 0.037 (150 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-10+24480C>T		intron_variant	Intron 3 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.-10+24480C>T		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5669 AN: 152174 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0372 AC: 5670 AN: 152292 Hom.: 150 Cov.: 32 AF XY: 0.0356 AC XY: 2648 AN XY: 74466

African (AFR) AF: 0.0102 AC: 426 AN: 41572

American (AMR) AF: 0.0304 AC: 465 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4832

European-Finnish (FIN) AF: 0.0347 AC: 368 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4131 AN: 68008

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.0168 Hom.: 10

Bravo AF: 0.0366

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.85
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs76211316; hg19: chr3-188083987;