3-188484794-G-T

Variant names:

• chr3-188484794-G-T
• rs1559814
• NM_001375462.1:c.306+90G>T

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.306+90G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 924,344 control chromosomes in the GnomAD database, including 445,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66516 hom., cov: 31)
  • Exomes 𝑓: 0.99 (378831 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.540
• Publications: 2 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=-0.81).
• BP6: Variant 3-188484794-G-T is Benign according to our data. Variant chr3-188484794-G-T is described in ClinVar as [Benign]. Clinvar id is 1275911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.306+90G>T		intron_variant	Intron 5 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.306+90G>T		intron_variant	Intron 5 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141275 AN: 151984 Hom.: 66480 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.972

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.985

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.949

GnomAD4 exome AF: 0.990 AC: 764278 AN: 772242 Hom.: 378831 AF XY: 0.991 AC XY: 404845 AN XY: 408620

African (AFR) AF: 0.756 AC: 14763 AN: 19534

American (AMR) AF: 0.981 AC: 39184 AN: 39962

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 19970 AN: 19970

East Asian (EAS) AF: 1.00 AC: 36458 AN: 36462

South Asian (SAS) AF: 0.987 AC: 66443 AN: 67288

European-Finnish (FIN) AF: 1.00 AC: 46602 AN: 46616

Middle Eastern (MID) AF: 0.977 AC: 4192 AN: 4292

European-Non Finnish (NFE) AF: 0.999 AC: 499943 AN: 500538

Other (OTH) AF: 0.977 AC: 36723 AN: 37580

GnomAD4 genome AF: 0.929 AC: 141369 AN: 152102 Hom.: 66516 Cov.: 31 AF XY: 0.932 AC XY: 69342 AN XY: 74390

African (AFR) AF: 0.762 AC: 31524 AN: 41392

American (AMR) AF: 0.964 AC: 14748 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5165 AN: 5166

South Asian (SAS) AF: 0.985 AC: 4754 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10626

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67908 AN: 68012

Other (OTH) AF: 0.949 AC: 2007 AN: 2114

Alfa AF: 0.950 Hom.: 8799

Bravo AF: 0.918

Asia WGS AF: 0.962 AC: 3347 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

- -

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	-0.81
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		0.54
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: rs1559814; hg19: chr3-188202582;