3-188524913-T-G

Variant names:

• chr3-188524913-T-G
• rs138209867
• NM_001375462.1:c.429+126T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375462.1(LPP):​c.429+126T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 139,178 control chromosomes in the GnomAD database, including 33,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (33517 hom., cov: 21)
  • Exomes 𝑓: 0.79 (140508 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-188524913-T-G is Benign according to our data. Variant chr3-188524913-T-G is described in ClinVar as [Benign]. Clinvar id is 1182900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.429+126T>G		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+126T>G		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 94089 AN: 139110 Hom.: 33516 Cov.: 21

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.693

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.786 AC: 349556 AN: 444612 Hom.: 140508 AF XY: 0.780 AC XY: 178634 AN XY: 228916

African (AFR) AF: 0.464 AC: 4189 AN: 9032

American (AMR) AF: 0.719 AC: 9578 AN: 13320

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 7314 AN: 10942

East Asian (EAS) AF: 0.867 AC: 23316 AN: 26880

South Asian (SAS) AF: 0.688 AC: 18030 AN: 26222

European-Finnish (FIN) AF: 0.727 AC: 21833 AN: 30052

Middle Eastern (MID) AF: 0.703 AC: 1441 AN: 2050

European-Non Finnish (NFE) AF: 0.813 AC: 246388 AN: 302878

Other (OTH) AF: 0.752 AC: 17467 AN: 23236

GnomAD4 genome AF: 0.676 AC: 94105 AN: 139178 Hom.: 33517 Cov.: 21 AF XY: 0.670 AC XY: 44694 AN XY: 66658

African (AFR) AF: 0.444 AC: 16644 AN: 37482

American (AMR) AF: 0.735 AC: 9941 AN: 13534

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2210 AN: 3362

East Asian (EAS) AF: 0.888 AC: 4388 AN: 4944

South Asian (SAS) AF: 0.696 AC: 2902 AN: 4168

European-Finnish (FIN) AF: 0.688 AC: 5340 AN: 7758

Middle Eastern (MID) AF: 0.744 AC: 201 AN: 270

European-Non Finnish (NFE) AF: 0.780 AC: 50624 AN: 64894

Other (OTH) AF: 0.696 AC: 1321 AN: 1898

Alfa AF: 0.564 Hom.: 1292

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.33
PhyloP100		1.2
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: rs138209867; hg19: chr3-188242701; COSMIC: COSV57082383; COSMIC: COSV57082383;