ENST00000520959.5:c.-140-18800C>T

Variant names:

• chr8-19929380-C-T
• rs7816032
• ENST00000520959.5:c.-140-18800C>T

Variant summary

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

The ENST00000520959.5(LPL):​c.-140-18800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 146,328 control chromosomes in the GnomAD database, including 11,076 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 0.33 (11076 hom., cov: 28)
• Consequence: LPL ENST00000520959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 15 publications found

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

LPL Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000520959.5	c.-140-18800C>T		intron_variant	Intron 1 of 4	4		ENSP00000428496.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 48688 AN: 146242 Hom.: 11049 Cov.: 28

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.333 AC: 48758 AN: 146328 Hom.: 11076 Cov.: 28 AF XY: 0.326 AC XY: 23249 AN XY: 71392

African (AFR) AF: 0.652 AC: 24222 AN: 37124

American (AMR) AF: 0.193 AC: 2882 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 840 AN: 3460

East Asian (EAS) AF: 0.160 AC: 820 AN: 5122

South Asian (SAS) AF: 0.285 AC: 1334 AN: 4674

European-Finnish (FIN) AF: 0.167 AC: 1728 AN: 10344

Middle Eastern (MID) AF: 0.264 AC: 76 AN: 288

European-Non Finnish (NFE) AF: 0.238 AC: 16070 AN: 67466

Other (OTH) AF: 0.291 AC: 593 AN: 2036

Alfa AF: 0.266 Hom.: 25346

Bravo AF: 0.357

Asia WGS AF: 0.255 AC: 884 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.30
PhyloP100		-0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7816032; hg19: chr8-19786891;