NM_001375462.1:c.-9-922C>T

Variant names:

• chr3-188405190-C-T
• rs2049218
• NM_001375462.1:c.-9-922C>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.-9-922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,120 control chromosomes in the GnomAD database, including 10,634 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 0.34 (10634 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-9-922C>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.-9-922C>T		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52245 AN: 152002 Hom.: 10642 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.343 AC: 52232 AN: 152120 Hom.: 10634 Cov.: 32 AF XY: 0.341 AC XY: 25343 AN XY: 74344

African (AFR) AF: 0.120 AC: 4988 AN: 41508

American (AMR) AF: 0.403 AC: 6156 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1627 AN: 5154

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4826

European-Finnish (FIN) AF: 0.364 AC: 3850 AN: 10576

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30940 AN: 67984

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.361 Hom.: 2151

Bravo AF: 0.338

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		-0.31
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: rs2049218; hg19: chr3-188122978;