rs3817462

Positions:

• chr3-188759802-A-G
• chr3-188759802-A-T

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.1241-311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,150 control chromosomes in the GnomAD database, including 956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (956 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.304

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=-0.84).
• BP6: Variant 3-188759802-A-G is Benign according to our data. Variant chr3-188759802-A-G is described in ClinVar as [Benign]. Clinvar id is 1265876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPP	NM_001375462.1	c.1241-311A>G		intron_variant		ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.1241-311A>G		intron_variant		1	NM_001375462.1	ENSP00000478901	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15473 AN: 152032 Hom.: 951 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0929

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

GnomAD4 genome AF: 0.102 AC: 15487 AN: 152150 Hom.: 956 Cov.: 32 AF XY: 0.105 AC XY: 7831 AN XY: 74374

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0924

Alfa AF: 0.109 Hom.: 1378

Bravo AF: 0.0912

Asia WGS AF: 0.168 AC: 583 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3817462; hg19: chr3-188477590;