rs1800590

Positions:

• chr8-19939160-T-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000524029.5(LPL):​c.-153-128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 516,462 control chromosomes in the GnomAD database, including 3,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (3135 hom., cov: 32)
  • Exomes 𝑓: 0.029 (859 hom.)
• Consequence: LPL ENST00000524029.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 0.707

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 8-19939160-T-G is Benign according to our data. Variant chr8-19939160-T-G is described in ClinVar as [Benign]. Clinvar id is 362399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19939160-T-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000520959.5	c.-140-9020T>G		intron_variant		4		ENSP00000428496
LPL	ENST00000522701.5	c.-218-63T>G		intron_variant		4		ENSP00000428557
LPL	ENST00000524029.5	c.-153-128T>G		intron_variant		4		ENSP00000428237

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18284 AN: 151894 Hom.: 3114 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0925

GnomAD4 exome AF: 0.0290 AC: 10563 AN: 364450 Hom.: 859 Cov.: 0 AF XY: 0.0279 AC XY: 5298 AN XY: 190104

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0205

Gnomad4 EAS exome AF: 0.000575

Gnomad4 SAS exome AF: 0.0350

Gnomad4 FIN exome AF: 0.00232

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.0453

GnomAD4 genome AF: 0.121 AC: 18349 AN: 152012 Hom.: 3135 Cov.: 32 AF XY: 0.117 AC XY: 8697 AN XY: 74332

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.0911

Alfa AF: 0.0455 Hom.: 729

Bravo AF: 0.136

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 27, 2019	This variant is associated with the following publications: (PMID: 25566792, 27055971, 9017514, 18922999) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hyperlipoproteinemia, type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hyperlipidemia, familial combined, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800590; hg19: chr8-19796671;