rs4449306

Positions:

• chr3-188234588-A-C
• chr3-188234588-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.-67+9061A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,004 control chromosomes in the GnomAD database, including 19,964 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 0.51 (19964 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.-67+9061A>C		intron_variant		ENST00000617246.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.-67+9061A>C		intron_variant		1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76739 AN: 151884 Hom.: 19969 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.505 AC: 76763 AN: 152004 Hom.: 19964 Cov.: 32 AF XY: 0.505 AC XY: 37515 AN XY: 74302

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.542

Alfa AF: 0.453 Hom.: 2298

Bravo AF: 0.499

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.55

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: rs4449306; hg19: chr3-187952376;