rs200398269

Variant names:

• chr3-188524881-TTCCTTCCTTCCGTCCG-T
• rs200398269
• NM_001375462.1:c.429+106_429+121delGTCCGTCCTTCCTTCC

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+121delGTCCGTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 634,180 control chromosomes in the GnomAD database, including 94,438 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 0.55 (12423 hom., cov: 0)
  • Exomes 𝑓: 0.47 (82015 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.862
• 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 3-188524881-TTCCTTCCTTCCGTCCG-T is Benign according to our data. Variant chr3-188524881-TTCCTTCCTTCCGTCCG-T is described in ClinVar as [Benign]. Clinvar id is 1234700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 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+121delGTCCGTCCTTCCTTCC		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+95_429+110delTCCTTCCTTCCGTCCG		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 54647 AN: 99238 Hom.: 12433 Cov.: 0

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.534

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.549

GnomAD4 exome AF: 0.467 AC: 249732 AN: 534910 Hom.: 82015 AF XY: 0.462 AC XY: 126291 AN XY: 273478

African (AFR) AF: 0.193 AC: 2141 AN: 11120

American (AMR) AF: 0.438 AC: 7191 AN: 16436

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 4582 AN: 11498

East Asian (EAS) AF: 0.832 AC: 21697 AN: 26080

South Asian (SAS) AF: 0.357 AC: 10999 AN: 30836

European-Finnish (FIN) AF: 0.385 AC: 13576 AN: 35240

Middle Eastern (MID) AF: 0.327 AC: 888 AN: 2714

European-Non Finnish (NFE) AF: 0.472 AC: 176883 AN: 374800

Other (OTH) AF: 0.450 AC: 11775 AN: 26186

GnomAD4 genome AF: 0.550 AC: 54642 AN: 99270 Hom.: 12423 Cov.: 0 AF XY: 0.553 AC XY: 26216 AN XY: 47412

African (AFR) AF: 0.391 AC: 7653 AN: 19554

American (AMR) AF: 0.593 AC: 6232 AN: 10502

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1276 AN: 2414

East Asian (EAS) AF: 0.874 AC: 4222 AN: 4828

South Asian (SAS) AF: 0.561 AC: 1636 AN: 2918

European-Finnish (FIN) AF: 0.550 AC: 3146 AN: 5722

Middle Eastern (MID) AF: 0.542 AC: 103 AN: 190

European-Non Finnish (NFE) AF: 0.574 AC: 29394 AN: 51198

Other (OTH) AF: 0.549 AC: 746 AN: 1358

Alfa AF: 0.284 Hom.: 2

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
PhyloP100		0.86
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: rs200398269; hg19: chr3-188242669;