3-188406566-C-A

Variant names:

• chr3-188406566-C-A
• rs1559810
• NM_001375462.1:c.193+253C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001375462.1(LPP):​c.193+253C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,996 control chromosomes in the GnomAD database, including 10,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10963 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.108
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-188406566-C-A is Benign according to our data. Variant chr3-188406566-C-A is described in ClinVar as [Benign]. Clinvar id is 1269445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.193+253C>A		intron_variant	Intron 4 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.193+253C>A		intron_variant	Intron 4 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55925 AN: 151878 Hom.: 10948 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.368 AC: 55979 AN: 151996 Hom.: 10963 Cov.: 32 AF XY: 0.375 AC XY: 27836 AN XY: 74274

African (AFR) AF: 0.225 AC: 9323 AN: 41468

American (AMR) AF: 0.435 AC: 6648 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2208 AN: 5164

South Asian (SAS) AF: 0.546 AC: 2625 AN: 4812

European-Finnish (FIN) AF: 0.479 AC: 5040 AN: 10532

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27587 AN: 67968

Other (OTH) AF: 0.395 AC: 832 AN: 2108

Alfa AF: 0.396 Hom.: 51237

Bravo AF: 0.355

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.41
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs1559810; hg19: chr3-188124354;