rs11923721

Positions:

• chr3-188382400-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375462.1(LPP):​c.-9-23712A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 152,246 control chromosomes in the GnomAD database, including 285 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 0.052 (285 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.-9-23712A>T		intron_variant		ENST00000617246.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.-9-23712A>T		intron_variant		1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7872 AN: 152126 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0862

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0517 AC: 7877 AN: 152246 Hom.: 285 Cov.: 32 AF XY: 0.0548 AC XY: 4077 AN XY: 74438

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.0433

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0512 Hom.: 29

Bravo AF: 0.0491

Asia WGS AF: 0.166 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.5
DANN	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs11923721; hg19: chr3-188100188;