chr3-188406031-T-G

Variant names:

• chr3-188406031-T-G
• rs3732911
• NM_001375462.1:c.-9-81T>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.-9-81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,247,090 control chromosomes in the GnomAD database, including 505,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (51998 hom., cov: 32)
  • Exomes 𝑓: 0.91 (453307 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.847
• Publications: 6 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=-0.85).
• BP6: Variant 3-188406031-T-G is Benign according to our data. Variant chr3-188406031-T-G is described in ClinVar as [Benign]. Clinvar id is 1266998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-9-81T>G		intron_variant	Intron 3 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.-9-81T>G		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123143 AN: 152012 Hom.: 51975 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.849

GnomAD4 exome AF: 0.907 AC: 993483 AN: 1094960 Hom.: 453307 AF XY: 0.907 AC XY: 497511 AN XY: 548496

African (AFR) AF: 0.546 AC: 13604 AN: 24900

American (AMR) AF: 0.924 AC: 28843 AN: 31212

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 16901 AN: 18584

East Asian (EAS) AF: 0.786 AC: 29031 AN: 36914

South Asian (SAS) AF: 0.864 AC: 55433 AN: 64128

European-Finnish (FIN) AF: 0.887 AC: 44140 AN: 49760

Middle Eastern (MID) AF: 0.903 AC: 3273 AN: 3624

European-Non Finnish (NFE) AF: 0.929 AC: 760429 AN: 818680

Other (OTH) AF: 0.887 AC: 41829 AN: 47158

GnomAD4 genome AF: 0.810 AC: 123209 AN: 152130 Hom.: 51998 Cov.: 32 AF XY: 0.811 AC XY: 60294 AN XY: 74370

African (AFR) AF: 0.551 AC: 22846 AN: 41452

American (AMR) AF: 0.900 AC: 13762 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3144 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3915 AN: 5160

South Asian (SAS) AF: 0.864 AC: 4154 AN: 4808

European-Finnish (FIN) AF: 0.880 AC: 9324 AN: 10598

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63090 AN: 68024

Other (OTH) AF: 0.851 AC: 1798 AN: 2114

Alfa AF: 0.842 Hom.: 13704

Bravo AF: 0.798

Asia WGS AF: 0.770 AC: 2677 AN: 3478

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

- -

Nov 12, 2018

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	-0.85
CADD	Benign	4.3
DANN	Benign	0.34
PhyloP100		0.85
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: rs3732911; hg19: chr3-188123819;