chr3-188524885-TTCCTTCCGTCCG-T

Variant names:

• chr3-188524885-TTCCTTCCGTCCG-T
• rs542563933
• NM_001375462.1:c.429+106_429+117delGTCCGTCCTTCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001375462.1(LPP):​c.429+106_429+117delGTCCGTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 250,740 control chromosomes in the GnomAD database, including 10,311 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (5588 hom., cov: 0)
  • Exomes 𝑓: 0.33 (10311 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 3-188524885-TTCCTTCCGTCCG-T is Benign according to our data. Variant chr3-188524885-TTCCTTCCGTCCG-T is described in ClinVar as [Benign]. Clinvar id is 1260569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.429+106_429+117delGTCCGTCCTTCC		intron_variant	Intron 6 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.429+99_429+110delTCCTTCCGTCCG		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 36947 AN: 71104 Hom.: 5585 Cov.: 0

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.328 AC: 82334 AN: 250740 Hom.: 10311 AF XY: 0.337 AC XY: 43540 AN XY: 129082

African (AFR) AF: 0.185 AC: 1480 AN: 8016

American (AMR) AF: 0.282 AC: 2093 AN: 7416

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 2531 AN: 6270

East Asian (EAS) AF: 0.411 AC: 967 AN: 2352

South Asian (SAS) AF: 0.353 AC: 5468 AN: 15478

European-Finnish (FIN) AF: 0.443 AC: 8202 AN: 18528

Middle Eastern (MID) AF: 0.361 AC: 543 AN: 1504

European-Non Finnish (NFE) AF: 0.315 AC: 56158 AN: 178258

Other (OTH) AF: 0.379 AC: 4892 AN: 12918

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.519 AC: 36966 AN: 71164 Hom.: 5588 Cov.: 0 AF XY: 0.516 AC XY: 17245 AN XY: 33422

African (AFR) AF: 0.407 AC: 7195 AN: 17694

American (AMR) AF: 0.536 AC: 3551 AN: 6626

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 931 AN: 1768

East Asian (EAS) AF: 0.474 AC: 147 AN: 310

South Asian (SAS) AF: 0.536 AC: 1095 AN: 2044

European-Finnish (FIN) AF: 0.530 AC: 2123 AN: 4004

Middle Eastern (MID) AF: 0.564 AC: 97 AN: 172

European-Non Finnish (NFE) AF: 0.568 AC: 20975 AN: 36928

Other (OTH) AF: 0.533 AC: 551 AN: 1034

Alfa AF: 0.236 Hom.: 0

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs542563933; hg19: chr3-188242673;