3-188162659-T-C

Variant names:

• chr3-188162659-T-C
• rs1679195
• NM_001375462.1:c.-190+8407T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375462.1(LPP):​c.-190+8407T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,984 control chromosomes in the GnomAD database, including 32,378 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32378 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• 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]

ENSG00000308437 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-190+8407T>C		intron_variant	Intron 1 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.-190+8407T>C		intron_variant	Intron 1 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98734 AN: 151864 Hom.: 32352 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.650 AC: 98810 AN: 151984 Hom.: 32378 Cov.: 32 AF XY: 0.644 AC XY: 47844 AN XY: 74254

African (AFR) AF: 0.700 AC: 28994 AN: 41440

American (AMR) AF: 0.695 AC: 10624 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3637 AN: 5148

South Asian (SAS) AF: 0.527 AC: 2534 AN: 4812

European-Finnish (FIN) AF: 0.594 AC: 6267 AN: 10544

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42982 AN: 67980

Other (OTH) AF: 0.624 AC: 1313 AN: 2104

Alfa AF: 0.628 Hom.: 48063

Bravo AF: 0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		0.14
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: rs1679195; hg19: chr3-187880447;