rs6444285

Variant names:

• chr3-188399998-C-T
• rs6444285
• NM_001375462.1:c.-9-6114C>T

Variant summary

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

The NM_001375462.1(LPP):​c.-9-6114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,004 control chromosomes in the GnomAD database, including 29,175 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 0.61 (29175 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-9-6114C>T		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.-9-6114C>T		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92235 AN: 151892 Hom.: 29136 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.607 AC: 92335 AN: 152004 Hom.: 29175 Cov.: 32 AF XY: 0.609 AC XY: 45277 AN XY: 74298

African (AFR) AF: 0.787 AC: 32614 AN: 41464

American (AMR) AF: 0.565 AC: 8630 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3280 AN: 5162

South Asian (SAS) AF: 0.655 AC: 3147 AN: 4808

European-Finnish (FIN) AF: 0.603 AC: 6364 AN: 10556

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34957 AN: 67956

Other (OTH) AF: 0.581 AC: 1224 AN: 2108

Alfa AF: 0.564 Hom.: 3105

Bravo AF: 0.612

Asia WGS AF: 0.654 AC: 2272 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.51
PhyloP100		-1.8
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: rs6444285; hg19: chr3-188117786;