3-188406031-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001375462.1(LPP):c.-9-81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,247,090 control chromosomes in the GnomAD database, including 505,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (51998 hom., cov: 32)
  • Exomes 𝑓: 0.91 (453307 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.847

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-188406031-T-G is Benign according to our data. Variant chr3-188406031-T-G is described in ClinVar as [Benign]. Clinvar id is 1266998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.-9-81T>G		intron_variant		ENST00000617246.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.-9-81T>G		intron_variant		1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123143 AN: 152012 Hom.: 51975 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.849

GnomAD4 exome AF: 0.907 AC: 993483 AN: 1094960 Hom.: 453307 AF XY: 0.907 AC XY: 497511 AN XY: 548496

Gnomad4 AFR exome AF: 0.546

Gnomad4 AMR exome AF: 0.924

Gnomad4 ASJ exome AF: 0.909

Gnomad4 EAS exome AF: 0.786

Gnomad4 SAS exome AF: 0.864

Gnomad4 FIN exome AF: 0.887

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.810 AC: 123209 AN: 152130 Hom.: 51998 Cov.: 32 AF XY: 0.811 AC XY: 60294 AN XY: 74370

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.851

Alfa AF: 0.848 Hom.: 13578

Bravo AF: 0.798

Asia WGS AF: 0.770 AC: 2677 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.3
Dann	Benign	0.34

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: rs3732911; hg19: chr3-188123819;