3-188524913-T-A

Variant names:

• chr3-188524913-T-A
• rs138209867
• NM_001375462.1:c.429+126T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001375462.1(LPP):​c.429+126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 140,042 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00017 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00016 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS2: High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.429+126T>A		intron_variant	Intron 6 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.429+126T>A		intron_variant	Intron 6 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 24 AN: 139968 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000221

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000202

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.000153

Gnomad OTH AF: 0.000527

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000159 AC: 71 AN: 446072 Hom.: 3 AF XY: 0.000148 AC XY: 34 AN XY: 229730

African (AFR) AF: 0.000329 AC: 3 AN: 9116

American (AMR) AF: 0.000224 AC: 3 AN: 13380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11000

East Asian (EAS) AF: 0.00 AC: 0 AN: 26914

South Asian (SAS) AF: 0.0000759 AC: 2 AN: 26362

European-Finnish (FIN) AF: 0.0000662 AC: 2 AN: 30194

Middle Eastern (MID) AF: 0.000975 AC: 2 AN: 2052

European-Non Finnish (NFE) AF: 0.000181 AC: 55 AN: 303738

Other (OTH) AF: 0.000172 AC: 4 AN: 23316

GnomAD4 genome AF: 0.000171 AC: 24 AN: 140042 Hom.: 0 Cov.: 21 AF XY: 0.000134 AC XY: 9 AN XY: 67118

African (AFR) AF: 0.000212 AC: 8 AN: 37740

American (AMR) AF: 0.000220 AC: 3 AN: 13612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.000202 AC: 1 AN: 4948

South Asian (SAS) AF: 0.00 AC: 0 AN: 4216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7844

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.000153 AC: 10 AN: 65252

Other (OTH) AF: 0.000522 AC: 1 AN: 1916

Alfa AF: 0.00 Hom.: 1292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.35
PhyloP100		1.2

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: rs138209867; hg19: chr3-188242701;