Variant chr8-19939160-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.707

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
LPL	ENST00000520959.5 linkuse as main transcript	c.-140-9020T>G	intron_variant	4
LPL	ENST00000522701.5 linkuse as main transcript	c.-218-63T>G	intron_variant	4
LPL	ENST00000524029.5 linkuse as main transcript	c.-153-128T>G	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18284

AN:

151894

Hom.:

3114

Cov.:

show subpopulations

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.:

AF XY:

0.0279

AC XY:

5298

AN XY:

190104

show subpopulations

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.:

AF XY:

0.117

AC XY:

8697

AN XY:

74332

show subpopulations

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:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over